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331 Cards in this Set
- Front
- Back
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Pox
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dsDNA
Complex neurocapsid Envelope D Replication Smallpox, molluscum |
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HAV
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Picornavirus
Naked Accute Fulminant |
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VZV
Clinical Features |
- 1o, varicella or chickenpox – systemic / disseminated viral disease
- reactivated, zoster or shingles - localized viral disease w/ neuronal spread to an affected dermatome |
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Zoonosis
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- spread from animals to humans (dead end host, we are not reservoirs)
- more than 50% of the viruses known to infect man are zoonotic - spread by vertebrates by biting, contaminated excreta - also spread by invertebrates, like mosquitoes, ticks, sandflies |
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Arthropod-Borne Encephalitis Viruses
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- must replicate in mosquito gut then move to salivary glad prior to transmissions
- peak is mid to late summer - no human to human spread - human viremias insufficient to let humans be the reservoir - Alphavirus genus of the family Togaviridae and the Flaviviridae family |
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Measles
Clinical features |
- respiratory exposure
- 10-14 day incubation - then 'ratcheting' high fever, cough, coryza and conjunctivitis - rash first on head and neck - unique red lesions (Koplik's spots) with white centers, appear on buccal mucosa |
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upper respiratory tract infections
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- common cold viruses (adenoviruses, non-SARS coronaviruses and rhinoviruses)
- replicate in epi surface of nasal mucosa - primarily in columnar and ciliated epi cells |
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Herpes
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dsDNA
Incosahedral neurocapsid Envelope D Replication HSV-1, HSV-2, VZV, CMV, Roseola (HHV-6, 7) |
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HBV
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Hepadnavirus
Envelope Accute to Chronic Fulminant |
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VZV
Chickenpox |
- mild febrile illness, disseminated vesicular rash of clear blisters w/ irregular red margin – resolved in a few wks
- macules -> papules -> vesicles -> pustules -> scabs - headache and malaise -> pruritic rash -> fever - Complications are 2o infections of lesions, post-infectious encephalomyelitis, pneumonia if immunocomp (in adults form fusion cell to cell spread, Reye’s syndrome |
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Emerging Zoonotic Viruses
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- most established for years in small, isolated animal populations
- Viral changes - reassortment (influenza), recombination (WEE virus), point mutation (chicken influenza) - travel (smallpox, syphilis, dengue), or behavior (STDs) - Vector changes - mosquitoes change range (yellow fever), birds migrate (West Nile virus) - Environment – irrigation (Rift Valley Fever), agriculture (Argentine HF), natural climate changes |
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Alphaviruses
Types |
- *Eastern Equine Encephalitis (EEE)*
- Western Equine Encephalitis (WEE) - Venezuelan Equine Encephalitis (VEE) |
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Measles
Complications |
- encephalomyelitis
- 1o measles or giant-cell pneumonia in immunodef - 2o bacterial pneumonia - keratoconjunctivitis in kids with nutritional deficiencies - subacute sclerosing panencephalitis (SSPE) - rare, follows 7-10 years after 1o |
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lower respiratory tract infections
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- paramyxoviruses (parainfluenza virus, respiratory syncytial virus, and human metapneumovirus
- myxoviruses (influenza) - SARS - coronavirus - primarily cuase bronchitis, acute laryngotracheobronchitis (croup), bronchiolitis and pneumonia |
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Adeno
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dsDNA
Incosahedral neurocapsid No Envelope D Replication |
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HCV
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Flavivirus
Envelope Accute to Chronic Fulminant |
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VZV
Shingles |
- reactivation of latent VZV
- like chicken pox, but larger lesions on the dermatome innervated by infected sensory nerve - may be very painful - usually if immunosuppresed (so odds increase w/ age) - complication is post-herpetic neuralgia - hypersensitive to touch and T |
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Zoonotic Viruses
Pathogenesis |
virus enters the body and replicates locally -> transient viremia -> infection of RES -> secondary viremia -> prodromal symptoms of fever, chills, headache, muscle ache, malaise -> after incubation period (2-14 days), other organs can infect -> more serious disease may occur
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Flaviviruses
Types |
- *St. Louis Encephalitis (SLE)*
- Japanese Encephalitis (JE) - Tick-Borne Encephalitis (TBE) - West Nile virus - Dengue virus |
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atypical measles
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- in persons who received killed measles vaccine during 1963-1967 then got infected
- atypical rash (no Koplik's), and serious pneumonitis |
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The Common Cold
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- acute resp illness - mild and self-limited
- inflam of the MMs of the nasopharynx (catarrh) - watery nasal discharge (which may contain sloughed columnar epithelial cells) - no fever - from rhinoviruses (100+ antigenic types) or coronaviruses (2) |
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papova
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dsDNA
Incosahedral neurocapsid No Envelope D Replication HPV |
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HDV
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Deltavirus
Envelope Accute to Chronic Fulminant |
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VZV
Properties of the Virus |
- like herpes virus
- enveloped - so easily inactivated - rapid replication and ease of transmission so hard to exploit |
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Zoonotic Viruses
Clinical Features |
- Inapparent infection is most common
- Fever, chills, headache, back pain, muscle and joint pain, with or without a rash appearing on the third or fourth day - if rash, slow convalescence (1o dengue fever, Colorado tick fever) and possibly hemorrhagic fever w/ blotches and orifice bleeding - may die from hypotensive shock (Dengue hemorrhagic fever/ Dengue shock syndrome, Ebola virus) - kidney targeted in hemorrhagic fever with renal syndrome - liver targeted in yellow fever - if acute respiratory syndrome w/ edema (SARS and Hanta pulmonary syndrome) - if encephalitis (EEE, WEE West Nile, SLE) |
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Alphavirus
Structure and Replication |
- Togaviridae family
- (+) sense ssRNA - Icosahedral nucleocapsid w/ 1 capsid protein w/ envelope (M and E) - Replication in cytoplasm with budding at PM |
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Measels
Virus properties |
- pleomorphic morbillivirus
- one molecule of (-) ssRNA - a viral-encoded RNA dependent RNA polymerase - a helical nucleocapsid - a lipoprotein envelope (know more about spikes) |
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Pharyngitis
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- acute inflammatory of pharynx
- sore and scratchy throat - edema and hyperemia of tonsils and pharyngeal MMs - from rhinoviruses usually |
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Polyoma
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dsDNA
Incosahedral neurocapsid No Envelope D Replication JC, BK |
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HEV
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Calicivirus
Naked Accute Fulminant |
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Pathogenesis of Primary Varicella-Zoster Infection
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- non-specific binding in the nasopharynx
- initial replication in resp epi -> LNs -> viremia to liver and spleen - 2o viremia mediated by PBMCs - transports cutaneous epi and resp mucosal sites (to spread) - w/ hematogenous and neural spread -> latent state in the sensory nerve ganglia - asymptomatically shed throughout the host’s life |
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Zoonotic Viruses
Diagnosis |
- difficult initially - easier as specific organs are targeted
- take a complete history - travel, pets, hobbies or jobs that might expose the Pt to animals or insects - Serology, PCR |
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Alphavirus
Epi |
- wild birds resivour - mosquito persistently infected
- along eastern seaboard - only a few cases a year, only 2% is Ab + in epidemics - Aedes albopictus, “Asian tiger mosquito”, is new - might let virus be a bigger problem, since it can feeds on birds and humans - human-to-human in aerosol in lab |
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Measels
Viral Spikes |
- one with hemagglutinating (H glycoprotein) activity
- one with cell-fusing (F glycoprotein) activity - F displayed on infected cell - Morbilliviruses have no neuraminidase activity on spikes and induce BOTH nuclear and cytoplasmic inclusion bodies - F is inactive precursor (Fo) cleaved by host in Golgi - envelope must fuse to host (via F) for infection, spread and multinucleate formation |
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Laryngitis
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- inflam of larynx MMs
- w/ common cold and influenza - lowering of the normal pitch, hoarseness, aphonia - from influenza, sometimes rhinoviruses, adenoviruses and parainfluenza viruses |
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Parvo
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ssDNA (+/-)
Incosahedral neurocapsid No Envelope D B19 |
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Laryngotracheobronchitis
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- croup
- acute, involving the larynx, trachea and bronchi - kids under four - high fever and blockage of the larynx and perhaps bronchi - dyspnea and creaking notes - typically due to one of the parainfluenza viruses |
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HGV etc
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Flavivirus
Envelope Chronic ? if fulminant |
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Zoonotic Viruses
Epidemiology of Hemorrhagic Fever Viruses |
- Vectors are rodents (Lassa fever, Hantavirus with renal syndrome, Argentine HF, Bolivian HF)
- Arthropods (Yellow fever, dengue, Rift Valley fever) - Ebola and Marburg viruses have unknown vectors - Human to human spread in Ebola, Marburg and Lassa fevers |
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Alphavirus
Clinical Features |
- Most subclinical
- febrile illness, may lead to encephalitis (50-75% fatal) - 20-12 day febrile illness, then fever, stiff neck, loss of consciousness - may go to seizures, coma and death or it may resolve |
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VZV
Epidemiology and Transmission |
- universal childhood infection
- spread by droplet - shed prior to symptoms - both are non-seasonal and non-epidemic - maternal protection for first six months - immunity primarily cell-mediated - 1o disease confers lifetime immunity to 1o, but shingles may develop due if immunocomp (age) – then protected from shingles |
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Measels
Pathogenesis |
- inhalation to RT mucosa ⇒
regional LNs ⇒ primary viremia - RE system ⇒ 2o viremia ⇒ lymphoid cells ⇒ lesions - rash from CMI response - infections probably involve CNS (usually asymptomatic) and growth curve is arrested |
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Hepadna
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pdsDNA
Incosahedral neurocapsid Envelope RT Replication HBV |
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bronchitis
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- inflam of tree
- ass. w/ generalized resp infection - hyperemic and edematous MM ⇒ increased bronchial secretions - cough to clear them - destruction of epi - accompanys a variety |
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Zoonotic Viruses
Treatment and Control of Hemorrhagic Fever Viruses |
- supportive – restore physiology and nutrition
- Ribavirin for arenaviruses (Lassa fever, Argentine and Bolivian HF) and bunyaviruses (hemorrhagic fever with renal syndrome) - Vaccines available for yellow fever and Rift Valley fever - Dengue vaccine most needed and most problematic – must get all 4 strains or it will increase your likelihood |
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Alphavirus
Pathogensis |
- moves from the blood ⇒ endothelial cells ⇒ nerve cells
- symptoms from viral action on nerve cells host imfla - EEE is cytolytic - apoptosis of infected cells - IFNs important |
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VZV
Diagnosis |
- based on presentation and contact history
- fluorescent Ab of lesions - culture provides the definitive diagnosis |
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HAV structure
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- same as poliovirus (but does NOT inactivate host cell
protein that associates with capped mRNAs) - Non-enveloped, icosahedral - 60 capsomers ( w/ VP1, VP2, VP3, VP4) |
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Measels
Immunity |
- only one serotype
- natural infection produces lifelong permanent immunity - neutralizing Ab directed at H - can cross placenta (6 mos) - agammaglobulinemics demonstrate a normal disease course - cell-mediated immunodef ⇒ persistent infection - concomitant depression of CMI to a wide variety of non-measles antigens |
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Retro
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ss+RNA
Incosahedral/Helical neurocapsid Envelope RT Replication HIV, HTLV-1 |
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Bronchiolitis
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- acute inflam and necrosis of the bronchiole epi
- before the age 2 - acute onset of wheezing and hyperaeration, tachypnea and resp distress - from resp syncitial virus |
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Pulmonary Zoonotic Viruses
Epidemiology |
- Sin Nombre (Hantaan virus) gets mice in Americas w/ no apparent ill effects - shed in urine and stool, transmitted to humans via aerosol
- SARS coronavirus from palm civet cats (probably) - both spread via human to human |
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Alphavirus
Treatment and Diagnosis |
- recovery due to development of Ab to envelope glycoproteins
- diagnosed by presentation or w/ serological tests like IgM ELISA - No vaccine or treatment |
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VZV
Prevention and Treatment |
- kids over 1 yr get one attenuated vaccine
- Acyclovir (or penciclovir) may terminate the viremia, reduce shedding, lessen severity - Zoster immune globulin given to exposed non-immunes |
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HAV genome
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- + sense, ssRNA that functions as mRNA
- translated as one ORF into polyprotein then processed by viral-coded proteases |
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Measels
Epi |
- very contagious from aerosolized droplets (sneeze)
- survives in droplets for hours - infected can spread 4 days before rash to 4 days after - hight mortality from lack of adequate nutrition and health care, its immunosuppressive - no animal reservoir - rapidly “burns itself out” in isolated rural areas |
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Picorna
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ss+RNA
Incosahedral neurocapsid No Envelope R Replication HAV, Polio, Coxsackie, ECHO, Rhinovirus |
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Pneumonia
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- inflammation of the lungs
- 6th death cause - destruction of ciliated epi - diffuse congestion of alveoli w/ erythrocytes - fluid may be seen - from RSV and parainfluenza viruses in children - influenza viruses in adults |
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Pulmonary Zoonotic Viruses
Treatment and Control |
- Rodent control, exposure control
- No drugs |
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Flaviviruses
Structure and Replication |
- Flaviviridae family, like HCV - can cause yellow fever
- (+) sense ssRNA - Icosahedral nucleocapsid w/ 1 capsid protein w/ envelope (M and E) - Replication in cytoplasm with budding at internal membranes |
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Cytomegalovirus
Clinical Features |
Presents differently among
- normal - fetuses - immunosuppressed |
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HAV translation
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- NTRs at the 5’ and 3’ ends.
- 5’ end not capped - ribosomes enter at IRES in 5’ then a Viral protein VPg covalently linked at 5’ and does RNA replication, and packaging, uncoating and penetration |
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Measels
Diagnosis |
Clinical symptoms
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Calici
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ss+RNA
Incosahedral neurocapsid No Envelope R Replication HEV, Norwalk |
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Adenoviruses
Structure and Replication |
- naked icosahedral particles
- linear dsDNA - several dozen serotypes, divided into subgroups (A-F) based on antigenicity RBC agglutinatation ability |
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Encephalitis Zoonotic Viruses
Epidemiology |
- EEE, WEE, SLE, West Nile
- Mosquito vectors, so usually seasonal - we are dead end host - Migratory birds play an important role |
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Cytomegalovirus
Immunocompetent |
- 1o unremarkable, usually in childhood
- most adults seropositive - in (-) adults, 1o from children shedding in urine, saliva and feces - adult 1o -> mild pharyngitis or EBV-like mono - after 1o, symptoms cease; viral shedding falls but may recur |
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Alphaviruses
Immunity |
- Protective humoral immunity directed to envelope proteins
- CTLs do inflam response |
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HAV-infected hepatocyte
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- translation of host mRNAs by usual cap-dependent process
- translation of viral mRNAs by CAP-independent process via IRES in 5’ NTR - not cytolytic - replication doesn't overstress the hepatocyte - IRES not efficient at loading host ribosomes |
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Measels
Treatment |
- no therapy
- A two day course of vitamin A reduces severity in kids - prevent w/ attenuated vaccine (MMR) |
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Astro
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ss+RNA
Icoashedreal Nucleocapsid No Enveolpe R replication |
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Adenoviruses
pathogenesis |
- genes E1A and E1B mediate transformation by deregulating cell cycle control by interacting w/ pRB gene
- not linked to human cancers - can maintain a long-term ass. w/ host by persisting in lymphocytes for years - discovered accidentally in cultured uninfected adenoidal tissue, from absence of immune surveillanc |
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Encephalitis Zoonotic Viruses
Treatment and Control |
- Rodent control, exposure control
- Supportive care - immune serum might help - no drugs or vaccine |
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Cytomegalovirus
Congenital Infection |
- if infected for the first time in pregnancy, may transmit to fetus
- in 1st trimester -> severe birth defects - if later, congenital abnormalities - (+) women w/ recurrent infection rarely transmit it - Affected babies may appear normal, but have progressive damage to NS, esp hearing - very common |
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Flaviviruses
Immunity |
- Protective humoral immunity directed to envelope proteins
- CTLs do inflam response |
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HAV Diagnosis
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- serology for anti-HAV specific IgM
- detection of an immune response at same time as onset of clinical symptoms implies immunopathogenesis |
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Measels Vaccine
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- give first dose at a min of of 12 months
- give second dose at least 12 months later; usually 4-6 yrs - window of susceptibility - more than >90% covered |
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Toga
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ss+RNA
Icoashedreal Nucleocapsid Enveolpe R replication WEE, VEE, EEE, Rubella(sphere nucleocap) |
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Adenoviruses
clinical features |
- can infect and replicate in RT, eye, GI, bladder, liver
- 5-10% of acute RI in kids - also causes ARD, a syndrome from fatigue and crowding among young military recruits |
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St. Louis Encephalitis Virus
Clinical Features |
- most prevalent arthropod encephalitis viruses in US
- most subclinical - may begin w/ fever, malaise, headache -> encephalitis, meningitis, & febrile headache - ESPbad for the elderly due to pre-existing conditions |
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Rabies
Pathogenesis |
- saliva of infected animal
- multiplies in striated muscle and CT (days -> months) - reaches nerve endings _> passively spread in axoplasm to spinal ganglia and replicates -> faster pace to the spinal cord -> brain -> salivary glands via efferent nerves |
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Cytomegalovirus
Immunosuppressed |
- may develop severe disease after infection
- interstitial pneumonia, retinitis, enteritis and disseminated disease - a high % of AIDS patients shed - ½ have infection at somepoint - primary post-transplant infection, esp bone marow |
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HAV pathogenesis
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- likely a GI site for primary replication ⇒ liver by viremia
- hepatocytes probably damaged by cytotoxic T and leads to release of virus into blood, - no chronic carrier state, lifelong immunity - no progression to carcinoma |
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Mumps
Clinical Features |
- 18 day incubation
- viremic spread to parotid and presents as swollen salivary glands - 1/3 infections subclinical - can involve the epithelial cells of organs |
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Flavi
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ss+RNA
Icoashedreal Nucleocapsid Enveolpe R replication HCV, SLE, Dengue, Yellow fever, West Nile |
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Adenoviruses
Epi |
- worldwide
- sporadic to epidemic - mostly fecal/oral in kids, but can occur via the resp route |
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St. Louis Encephalitis Virus
Epi |
- mosquitoes winter reservoirs in winter, transmission begins in spring w/ birds as host
- human disease peaks from July - Sept - 50/year - 5-15 year outbreak cycles |
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Rabies
Clinical Features |
- 2-8 wk incubation depending on amt of inoculum, virulence, proximity to neural tissue (head and neck wounds the worst)
- 2-4 day prodromal period - 1st fever, headache, malaise, sensations at the wound site - then increased irritability, anxiety, depression, sensitivity to sound and light - difficulty swallowing - generalized encephalitis develops and is always fatal |
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Cytomegalovirus
Properties of the Virus |
- like herpes (HHV-5)
- largest herpesviruses genome - it has a restricted host range - it is sensitive to heat, low pH, lipid solvents (envelope) |
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HAV immune response
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- humoral IgM - later supplanted by IgG
- CMI responds with cytotoxic lymphocytes - clinical symptoms after viral shedding stops - serum ALT, AST rise - all infected cells cleared from liver and replaced by new - resolution ⇒ recovery ⇒ immunity - in young, asymptomatic ⇒ response of less mature CMI?? |
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Mumps
Complications |
- orchitis in 25% of males, worse and more common if post-puberty -> sterility
- aseptic meningitis in up to 50%, usually subclinical |
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Corona
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ss+RNA
Helical Nucleocapsid Envelope R replication SARS, non-sars |
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Adenoviruses
Treatment |
- vaccines to prevent disease by certain adenovirus types
- vaccination -> asymptomatic virus replication in GI - not for civilians - concerns for spread of non-attenuated virus and oncogenic potential |
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St. Louis Encephalitis Virus
Diagnosis |
- consider if encephalitis, meningitis or febrile headache in July - September, esp old
- PCR of blood, CSF or tissue - IgM in serum or CSF by ELISA - Ab testing of paired sera - immunofluorp for SLE Ag in cells of urine sediment or CSF |
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Rabies
Epidemiology |
- in resource-poor nations, mainly from domesticated animals (dogs)
- in developed countries from wild animals (vaccination) - 74% in US from bats - rapidly increasing epidemic in SE US in raccoons and foxes |
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Cytomegalovirus
Pathogenesis and Immunity |
- outcome determined by host immunity
- 1o in salivary gland epi -> asymptomatic viremia and shedding |
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HAV epi
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- humans only reservoir
- hard to control since virus sheds in feces for two weeks before symptoms - most mild or asymptomatic - stable in the environment - spread person to person via fecal-oral spread during sex, esp anal sex - problem day care centers - fecal contam of source, esp water w/ shellfish - in food if poor hygene or uncooked fruits or gebbies |
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Mumps
Viral Properties |
- pleomorphic paramyxovirus
- transcription, replication and assembly in cytoplasm like the measles virus - envelope has 2 spikes - one with H and N activities, the other w/ F activity |
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Rhabdo
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ss-RNA
Helical Nucleocapsid Envelope R replication Rabies |
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Rhinovirus
Structure and replication |
- (+) polarity ssRNA
- naked icosahedral capsid - capsid from copies of 4 proteins, like picornavirus - 30-40% of winter colds - replication T sensitive at 37° - limits to URT |
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St. Louis Encephalitis Virus
Treatment |
- no vaccine, treatment limited to supportive therapy
- reduce of vector populations - hard to do since expansion of mosquito habitat, insecticide resistance, new vectors species |
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Rabies
Diagnosis |
- definitive diagnosis from post-mortem examination of the animal
- neck biopsy can be used in symptomatic humans - darkly-staining viral nucleocapsids (Negri bodies) in cytoplasm of CNS cells |
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Cytomegalovirus
Epidemiology and Transmission |
- ubiquitous, more in urbar areas
- humans only reservoir - in all body fluids, close contact transmits - (+) can shed for years - sources are daycare kids, immunocomp shedding more, (+) moms milk |
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HAV treatment
|
- practice proper hygiene
- Vaccine, need 2-3 doses of killed - recommended for travelers - required for some school entry, given to children at ≥ age 2 - no drugs available - used to give immune serum globulin to prevent effects, but now pooled gamma globulin is becoming low in anti-HAV |
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Mumps
Pathogenesis |
- replicates in URT, then to LNs ⇒ viremia
- replicates in the epi cells of various organs (parotid) - cell lysis then multi nucleated giant cells (cell fusion) |
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Paramyxo
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ss-RNA
Helical Nucleocapsid Envelope R replication Mumps, Measles, RSV, parainfluenza |
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Cytomegalovirus
Diagnosis |
- subclinical in most - misdiagnosed as EBV.
- likely the cause of mono if EBV negative - found in WBCs by immunofluorescence. - shell vial assay detects w/in within 24 hours. - in immunocomp - serology for IgM and IgG - in congenital - infant’s urine and saliva - in immunosup - culture a biopsy |
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West Nile Virus
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- severe meningoencephalitis in elderly in israel
- came to US in 1999, found in wild birds, horses and humans - 2002 outbreak, most cases from mosquito bite, some from transplants - blood is now screened - usually in old - if pregnant, rarely associated with spontaneous abortion and neonatal illness, but not birth defects - but intrauterine infection possible |
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Rabies
Prevention and Treatment |
- vaccination of domestic animals
- wound site immediately cleaned to and injected w/ human rabies hyperimmune globulin to neutralize slow growing virus - attempt to develop active immunity in the exposed person with a vaccine |
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HEV structure
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- + sense ssRNA; three ORFs - one translated as a polyprotein processed by a viral protease
- classified as a calicivirus (general similarity to HAV) |
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Coronavirus
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- (+) polarity ssRNA
- helical nucleocapsid w/ envelope containing 3 or 4 glycoproteins in spikes - pleomorphic shape - 20-30% of winter colds |
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Mumps
Immune response |
- only one serotype
- immunity lifelong - neutralizing Abs directed at the HN envelope protein - Ab in saliva signals the end of virus excretion - can cross placenta |
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Orthomyxo
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ss-*RNA
Helical Nucleocapsid Envelope R replication Influenza |
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Cytomegalovirus
Prevention and Treatment |
- no good treatment
- no viral TK, so no acyclovir or penciclovir - ganciclovir works (still analog of dG, but a viral kinase will phosphorylate it) |
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Transmissible Spongiform Encephalopathies (TSEs)
Kuru, Creutzfeld-Jakob Disease, and Mad Cow Disease (BSE) Clinical Features and Pathogenesis |
- transmitted by inoculation or ingestion of diseased nervous tissue
- incubation can last decades - death is usually months after symptoms appear - loss of motor control, dementia, wasting, with progressive loss of brain function -> death - large vacuoles in the cortex and cerebellum |
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The Picornaviridae family
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- genus Enterovirus
- poliomyelitis virus - echoviruses (enteric cytopathic human orphan virus) - enteroviruses - coxsackieviruses (Coxsackie, NY …site of first isolation) - genus Rhinovirus (including “cold” viruses) - genus Hepatovirus (hepatitis A virus) |
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Rhinovirus and Coronavirus
pathogenesis |
- confined to URT
- minimal and self-limiting - may set stage for more serious bacterial infections (sinusitis, OM) - only coronavirus can cause more serious disease in kids like bronchiolitis, bronchitis and pneumonia |
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HEV clinical features
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- fecal-oral spread - similar to HAV
- much higher incidence of fulminant hepatitis, with an especially high mortality (20%) in pregnant woman |
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Mumps
Epi |
- spread via aerosolized droplets, esp in winter and spring
- shed for 7-10 days, from 6 days prior to symptoms |
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Bunya
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ss-*RNA
Helical Nucleocapsid Envelope R replication Hanta |
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Poxviruses
Clinical Disease |
- Smallpox
- Vacinnia - Molluscum contagiosum - Zoonotic poxviruses |
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Transmissible Spongiform Encephalopathies (TSEs)
Kuru, Creutzfeld-Jakob Disease, and Mad Cow Disease (BSE) Properties of the Agent and Replication |
- prion disease - small, proteinaceous infectious particle that resists inactivation by procedures that modify nucleic acid
- the altered protein (PrPsc) forces normal proteins (PrPc) in alpha helices into abnormal or beta sheets -> fibrils and amyloid plaque - very hard to inactivate (remember the brains in lab) |
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Poliomyelitis
Structure |
- small, (+) ssRNA
- spherical, icosahedral, acid stable - poly (A) tail and a 5’ VPg - NTRs flank coding regions |
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Rhinovirus and Coronavirus
Immunity |
- strain specific immunity after infection
- lots of serotypes (over 100 r) - c immunity limited - can be re-infected w/in 2 years |
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HEV Pathogenesis
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- no chronic carrier state
- no progression to hepatocellular carcinoma |
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Mumps
Diagnosis |
- clinical symptoms alone
- swollen parotid - virus may be cultured - antiviral Abs may be found in the convalescent serum |
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Arena
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ss-*RNA
Helical Nucleocapsid Envelope R replication Lassa, LCM, the 2 HF's |
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Poxviruses
Clinical Disease Smallpox |
- eradication in 1977
- presented as either variola major or minor - rash is macules -> papules -> vesicles -> pustules -> crusts - major form of had 10 - 30% mortality, partly due to disruption in food production - Monkeypox in African is transmissible to human |
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|
Creutzfeldt-Jakob Disease
Epi |
- rapidly fatal, presenile dementia of old people
- memory loss w/ confusion, vertigo, blurred vision -> dementia and motor dsfunction - usually acquired sporadically, but some genetic from amyloid precursor protein mutation - can be transmitted by surgical instruments, transplanted dura and corenea - no immune response, no treatment , and no recovery or remission |
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|
Poliomyelitis
Replication |
- initially replicates in the human intestinal tract
- attaches to receptors (which determine tropism) - viropexis (RME) does penetration and uncoating - translation is cap-independent - cap-binding complex (CBC) shuts of host proteins - uses RNAdependentRNA polymerase - asymmetric, many (+) molecules made few (-) |
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Rhinovirus and Coronavirus
Epi |
- nose-hand-nose b/t people
- r can survive for hours on environmental surfaces - reducing spread via handwashing, ventilation |
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|
HEV Epi
|
- similar to HAV
- endemic in 3rd world from contamination of water - uncommon in US, only from going abroad - important to ask about pregnancies - its been found in US pigs, be careful w/ hog farms near water |
|
|
Mumps
Treatment |
- immunization with live attenuated vaccine (MMR)
- no antiviral therapy |
|
|
Filo
|
ss-RNA
Helical Nucleocapsid Envelope R replication Marburg, Ebola |
|
|
Poxviruses
Clinical Features Vaccinia |
- used as propylaxis of variola
- following subcutaneous inoculation is a papule - lesion has same pattern as smallpox w/out spreading |
|
|
Bovine Spongiform Encephalopathy (BSE)
|
- scrapie is a naturally occurring spongiform encephalopathy of sheep
- developed from feeding cattle scrapie-infected sheep by-products - Mad Cow Disease - may have adapted to be more stable in humans |
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|
Poliomyelitis
Clinical Features |
- most subclinical - malaise, fever, headache, nausea
- “abortive poliomyelitis”, as symptoms only last a few days - rarely can cause aseptic meningitis (resolves in 2-10 days) - rarely, paralytic polio - most significant paralysis presents w/in a few days, and most recovery is w/in 6 months - “progressive post-poliomyelitis muscle atrophy” - 25-40% have additional deterioration decades later from effects of aging |
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|
Rhinovirus and Coronavirus
Treatment |
- Capsid-binding antiviral agents (WIN compounds) prevent
virus binding and entry for R - Anti-receptor compounds against ICAM-1 - prevent R binding and entry - prevents, doesn't treat - adding soluble ICAM-1 receptor helps - fast resistace - hard to treat b/c no early clinical recognition, no rapid differentiation, short half-life - no vaccine |
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|
HEV Diagnosis
|
- clinical signs combined with history and exclusion
- serology requires special tests (available through CDC) |
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|
Rubella Clinical Features
|
- normally like measles
- 14-21 day incubation - most cases subclinical - starts w/ rash (face ⇒ extremities) and lasts 3 days - if acquired later in life (by males or non-pregnant females) its uncomplicated - if pregnant, congenital rubella syndrome and high risk of spontaneous abortion - congenital often results in hearing loss or cataracts - can take months to manifest - as kids, they can be carriers and shed |
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|
Delta
|
ss-RNA
? Nucleocapsid Envelope R replication HDV |
|
|
Poxviruses
Clinical Features Molluscum contagiosum |
- self-limiting infection of the skin
- small umbilicated nodules - may last from months to years - increased severity in AIDS iincreasing frequency in genital infections |
|
|
Variant Creutzfeldt-Jakob Disease (vCJD)
|
- like CJD, but ataxia and memory loss more common
- younger age group (16-45 years), mainly in UK - methionine homozygosity at position 129 of the prion protein predisposes to CJD, kuru, and vCJD - possibly from exposure to BSE - similar glycosylation patterns, abundant, distinct amyloid plaques in both, and mice inoculated w/ either show similar disease |
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Poliomyelitis
Pathogenesis |
- alimentary tract via mouth - shed in feces for several weeks
- 1o replication in OP mucosa, tonsils, LNs - ingested to gut and adjacent lymphoid tissue - 1o viremia infection of Peyer's patches and mesenteric LNs - spread to SC, meninges, and muscle - paralysis after 10 days - direct destruction of the neurons or edema-induced damage of the neurons (reversible) - fatal outcome if infection gets the CV centers of the medulla oblongata |
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|
Respiratory Syncytial Virus
Structure |
- irregular shape
- (-) sense ssRNA - helical nucleocapsid w/ envelope (3 spiky glycoproteins) |
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|
HEV Treatment
|
- supportive treatment only (no anti-viral therapy)
- recombinant vaccines are still under development |
|
|
Rubella Virus Properties
|
- spherical nucleocapsid w/ envelope - Togaviridae family
- no RNA-dependent RNA polymerase in the virion - one molecule of (+) RNA - replication and maturation are confined to the cytoplasm - infectious virions bud from the cytoplasmic membrane |
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|
HCV structure
|
- nucleocapsid protein
- E1 and E2 are glycoproteins present in the viral envelope - NS include proteases, and an RNA dependent RNA polymerase - substantial genetic heterogeneity - six genotypes (1, 2 and 3 are most prevalent in the US) and 100 subtypes |
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|
Reo
|
ds*RNA
Icosahedral necleocapsid No envelope R replication Rotovirus |
|
|
Poxviruses
Clinical Features Zoonotic poxviruses |
- transmitted by direct contact
- occupational hazard - self-limiting lesions on hands or face - orf virus of sheep or goats, and cowpox |
|
|
Poliomyelitis
Epidemiology |
- poliomyelitis not endemic (unlike other enteros) b/c of vaccination
- bad in Sub-Saharan Africa and South Asia - in US, only in immunocompromised vaccinees, imports, vaccinated contact |
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|
Respiratory Syncytial Virus
Replication |
- G glycoprotein binding initiated infection
- penetrates via envelope fusion w/ PM (F mediates) - events in cytoplasm - transcribed by virion associated polymerase - nucleocapsids bud through PM |
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|
HIV
Sturcture |
- retrovirus – enveloped, RNA
- uses reverse transcriptase, RNase H, integrase, protease |
|
|
Rubella
pathogenesis |
- droplets ⇒ nose and local LN
⇒ viremia ⇒ organs and skin - no fusion protein, so no cell to cell - viremia - shed for 1 week after rash - infection -> lifelong immun - Abs cross the placenta |
|
|
HCV genome
|
- + sense ssRNA
- no 5’ cap; IRES in 5’ NTR - no virion-associated polymerase - one ORF translated as one polyprotein then cleaved by cellular and viral proteases |
|
|
high fidelity replication
|
DNA based
|
|
|
Poxviruses
Properties |
- large, complex, dsDNA
- replication in the cytoplasm - have DNA-dependent RNA poly in nucleocapsids |
|
|
Non-poliomyelitis enteroviruses
Epidemiology |
- usually no pandemic, just periodic sweeping every few years
- most mild or asymptomatic - usually in kids in summer - lower socioeconomic areas - often found shellfish harvesting water |
|
|
Respiratory Syncytial Virus
Clinical Features |
- 4 to 5 day incubation
- 6-10 day recovery for kids - <1% mortality unless immunocompromised - bronchiolitis characterized by lymph infiltration & edema - pneumonia characterized by rales or infiltrates - no deepter than superficial layers of resp epi |
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|
HIV
Replication strategy |
- Attach via CD4 protein receptor (chemokine as a co-receptor to fuse)
- RT and RNase H copy in DNA, then that’s transported to the nucleus where integrase inserts viral DNA into host chromosome - large precursor proteins assemble then protease cleaves - RT and protease are current drug targets |
|
|
Rubella Epi
|
- springtime epidemics every few years - endemic worldwide
- unique togaviruses - it is neither infects nor is transmitted by arthropod - outbreaks due to gaps in our vaccine coverage are a concern |
|
|
HCV Clinical Features
|
- like acute HBV infection w/ lower serum ALT
- often sequential ‘episodes’ - many asymptomatic infections - 40% of chronic carriers later develop cirrhosis which progresses into carcinoma |
|
|
low fidelity replication
|
RNA based
RT based |
|
|
Poxviruses
Pathogenesis and Immunity |
- inhalation ->replication in URT, LRT -> infection of M’s -> LNs for replication and cell-associated viremia (asymptomatic and non-infectious)
- replication in the spleen and bone marrow -> 2o viremia and replication in dermis -> skin for symptoms, OP form spread |
|
|
Poliomyelitis
Diagnosis |
- clinical signs nondescript - use knowledge of a current epidemic
- specific viruses identified via immuno-serological techniques - appropriate specimens are stools, rectal and throat swabs - mixed infections of enteroviruses common |
|
|
Respiratory Syncytial Virus
Immunity |
- mediated by secretory Abs, serum Abs and cytotoxic T
- get maternal Abs - multiple re-infections does immunity in older children - secretory neutralizing IgA Abs better on nasal mucosa than serum, but not great - cellular immunity ok, but short-lived - local immunity most important in URT, serum Ab best in LRT |
|
|
HIV
Clinical Features and Pathogenesis |
- progressive loss of CD4+ helper Ts -> immunodef
- Acute Infection - levels of virus present w/in 6 months - some immune insult that can’t be repaired by controlling viral replication later on - Chronic infection - high rates of replication and immune clearance – sometimes and aggressive form uses a different co-receptor -> more rapid disease - CD4+ T cell count drops below 200 |
|
|
Rubella Diagnosis
|
- usually clinical symptoms
- tests for immune status of women of childbearing age - can be cultured in lab |
|
|
HCV pathogenesis
|
- damage to hepatocytes is apparently from cytotoxic T's and virus-induced cell death
- biopsies show most cells w/ no CPE, no HCV Ag or RNA, but bile duct damage, steatosis and lymphoid follicles - IFN response key for viral clearance - most become chronic, leading cause of chronic cirrhosis and requests for liver transplant - causes PHC - 40+% die |
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|
very low fidelity replication
|
HIV and HCV - every "clone" is different
|
|
|
Rubella Treatment
|
- vaccination of children
- medical people are often required to be immune - vaccine is very effective and long-lived |
|
|
Poxviruses
Epidemiology and Transmission |
- variola virus shed during acute infection
- outbreaks in rural area got all age groups - only kids in urban (frequent exposure) - monkeypox is relatively rare and less transmissible, but just as serious |
|
|
Poliomyelitis
Prevention and Treatment |
- vaccination is key (but none for other enteroviruses)
- isolation of infected - resistant to disinfectants |
|
|
Respiratory Syncytial Virus
Epi |
- severe in infants and kids, mild URT in adults - infants esp prone -> bronchiolitis and pneumonia
- most common viral thing in infants (2-7 mos), esp bad if premature - big immunosuppressed adults and elderly - all infected by age 2, adult re-infection common - 1o infection most severe |
|
|
HIV
Opportunistic infections – Fungal |
- Candida (oral -> esophagus)
- Pneumocystis carinii (pneumonia - PCP) - Cryptococcus neoformans (meningitis) - Histoplasma capsulatum (pneumonia or disseminated) |
|
|
HCV immunity
|
- virus undergoes “antigenic drift” within the patient - specific ab's promote the selective propagation of virus with variant antigens
- “Quasi-species” concept. - positive serology means on-going infection and viremia: not recovery |
|
|
(+) RNA
|
- replication: parental (+) -> (-) RNA -> progeny (+) RNA
- gene expression: parental (+) -> mRNA thats translated directly |
|
|
Human Herpesvirus 6 and 7
Clinical Features |
- 6th disease or "roseola" in kids under 2
- high fever and a red rash - resolves in 3-5 days without complications or sequelae, and most are asymptomatic - 50% of febrile episodes in infants due to HHV-6 - lifelong protection, so infection in immunocompetent adults is rare |
|
|
Poxviruses
Diagnosis |
- not part of differential diagnosis
- most related viruses ass. w/ animals or travel, take careful history |
|
|
Poliomyelitis
Killed vaccine advantages |
- can be combined w/ (DPT)
- no mutation - ok if immunodeficient - reduces spread of live polioviruses |
|
|
Respiratory Syncytial Virus
pathogenesis |
- transmitted by close contact
- aerosolized in large droplets of resp secretions - infected kids shed for 3 wks - can stay of surfaces for hrs - spread in hospitals and daycare is a major problem - mid-winter to late spring - handwashing prevents! |
|
|
HIV
Opportunistic infections – Protozoan |
- Cryptosporidium (gastroenteritis)
- Toxoplasma gondii (encephalitis) |
|
|
(-) RNA
|
- replication: parental (-) -> (+) RNA -> progeny (-) RNA
- gene expression: parental (-) -> (+) RNA that acts as mRNA |
|
|
Human Herpesvirus 6 and 7
Properties of the Virus |
- replication & structure like other herpesviruses
- icosahedral capsid and spiked envelope - latent after 1o infection - 1 case of virus-associated hemophagocytic syndrome (VAHS) from reactivation - prominent phago of BCs in bone marrow and LNs |
|
|
Poxviruses
Prevention and Treatment |
- vaccination for lab workers handling it
- eradication worked b/c humans only reservoir, 1 serotype, all symptomatic, predictable epidemics recovered patients recognized by lesions - vaccine very stable when dried and vaccinees marked by vaccination scar - encodes a (TK) that does not (P) ACV so ACV not effective |
|
|
HCV epi
|
- humans reservoir - ~1%
- blood-borne pathogen - ~80% prevalence in IV drug users - drugs, sex, childbirth, transfusion - blood banks now routinely use serology and an additional RT-PCR test - RF;s tattos and piercings - Sexual and vertical transmissions occur less frequently than with HBV |
|
|
Poliomyelitis
Killed vaccine disadvantages |
- low % develop Abs, so repeated boosters neede
- no intestinal immunity - expensive |
|
|
Respiratory Syncytial Virus
treatment |
- treat severe kids w/ humidified O2, bronchodilators and assisted ventilation
- IV IG in high risk cases - no vaccines, but live attenuated being tested - hard to make infant vaccine b/c of maternal antibody and the immune immaturity |
|
|
HIV
Opportunistic infections - Bacterial |
- Mycobacterium tuberculosis (pneumonia and/or disseminated)
- Mycobacterium avium complex (MAC, disseminated infection, fever) - higher susceptibility to common infections |
|
|
Parainfluenza Virus
Structure |
- (-) sense ssRNA
- virion-associated RNA polymerase - replicate in the cytoplasm |
|
|
Human Herpesvirus 6 and 7
Pathogenesis |
- respiratory route - oropharynx ⇒ many cell types
including lymphocytes (esp CD4), Ms, epi and endo cells - a tiny fraction of these cells become infected during childhood roseola |
|
|
dsRNA
|
- replication: parental dsRNA -> (+) RNA -> progeny dsRNA
- gene expression: parental dsRNA -> (+) RNA that acts as mRNA |
|
|
Rotaviruses
Properties and Replication |
- reovirus family, 11 pieces of dsRNA, so high rate of reassortment
- groups share cross reactive Ags (A, B, C in humans, A in US) - reassortment w/in groups - 3 layer icosahedral w/ spikes (must be cleaved to infect) - cytocidal, replicate in the intestinal epi cell cytoplasm |
|
|
HCV diagnosis
|
- Use ELISA for Ab's
- RT-PCR for viral RNA is now available |
|
|
Poliomyelitis
Live polio vaccine advantages |
- humoral and intestinal immunity (like natural)
- immunity lifelong - oral, works quickly - relatively inexpensive - uses of continued cell lines, no contaminants |
|
|
HIV
Opportunistic infections – Viral |
- cytomegalovirus (retinitis)
- herpes simplex virus (mucocutaneous lesions) - Epstein-Barr virus (oral hairy leukoplakia, lymphomas) - varicella-zoster virus (shingles) |
|
|
Parainfluenza Virus
Replication |
- encode a hemagglutinin / neuraminidase (HN) glycoprotein spike that binds sialic acid to attach and enter - high [sialic acid] in URT and LRT
- viral genome transcribed and nucleocapsids assemble in cytoplasm and bud through PM - encodes an (F) spike and forms syncytia |
|
|
Human Herpesvirus 6 and 7
Epi |
- transmitted by salivary droplets
- requires close contact - infection is universal - usually presents in infants soon after maternal Ab waned - most subclinical or febrile illnesses without the rash |
|
|
reverse transcriotion
|
- ss(+)RNA -> (via RT)
- (+)RNA and (-)DNA -> (via RNase H) - ss(-)DNA -> (via RT) - dsDNA |
|
|
Rotaviruses
Pathogenesis |
- ingested (fecal-oral) -> viruses replicate in the columnar epi -> villi lose the epi cells -> malabsorption -> diarrhea
- glycoprotein 4 may be enterotoxin -> diarrhea - die from dehydration - no residual damage if cleared of virus |
|
|
HCV treatment
|
- No vaccine
- No hyperimmune serum - IFNα licensed for therapy experience is mixed - can achieve suppression of viremia - new aggressive combo is interferon (injections) + ribavirin (oral) for 48 weeks -> ~40% have non-viremic with normal serum ALT esp for Genotypes 2 and 3 |
|
|
Poliomyelitis
Live vaccine disadvantages |
- may mutate -> neurovirulence
- spreads to other persons and environment - problem if immunodeficient - monkey testing |
|
|
HIV
Diagnosis |
- AIDS-defining illness in healthy person - then do western blot
- test positive for anti-HIV-1 Abs - then count CD4+ T and level of viral RNA - flu-like symptoms from acute HIV-1 - common symptoms so consider risk factors – no Abs but plasma RNA - After a known exposure – - After birth of a baby to an HIV infected mother - monitor for Abs or plasma RNA for 6 months - some starts administering therapy anyway |
|
|
Parainfluenza Virus
Clinical features |
- 2nd cause of LRT in kids
- the most common cause of croup in kids (esp type 1) - non-croup infections present as a hoarse cough w/ fever which resolves in 2-3 days |
|
|
replicating the dsDNA from RT
|
- dsDNA in nuc -> (via host DNA dep RNA poly II)
- mRNA in cyto -> (via RT and RNase H) - dsDNA in cyto |
|
|
Rotaviruses
Clinical Signs |
- subclinical to fatal diarrhea
- infants asymptomatic, maternal antibody - severe almost exclusively seen in the 6-24 months, as later infections are mild (unless immunocomp, but not big in HIV) - asymptomatic incubation for three days after vomiting - diarrhea begins later but then continues for up to a week - give supportive fluid therapy to resolve |
|
|
Human Herpesvirus 6 and 7
Diagnosis |
clinical presentation
|
|
|
HBV genome
|
- circular pdsDNA, w/ 4 overlaping ORFs w/ no non-coding bases
- 2 in-frame start codons -> Pre C, the signal peptide, is cleaved within Pre C near the carboxyl terminus of C -> HBe - Viral polymerase has priming domain, RTase, & RNase H and does RT w/in nucleocapsid - X gene encodes regulatory protein (not involved w/ viron |
|
|
Polyomaviruses
JC virus |
- PML, a progressively fatal, neurodegenerative disease
- due to SV 40 ('the vacuolating agent') – maybe from contaminated OPV vaccine - Inclusion bodies seen in brain - 1-10% of AIDS patients - distantly related to SV 40 |
|
|
HIV
Treatment |
- inhibitors include Nucleoside analogs (AZT, 3TC, ddI, ddC) are chain terminatorys - Non-nucleoside RT inhibitors (NNRT) bind RT to inactivate - Protease inhibitors - make sure its strong, wont develop resistance (use combos), and is tolerated
- if 50 copies/ml of plasma, probably no progress or resistance - AZT, 3TC and the protease inhibitor indinavir usually will do this - if suppression is incomplete, resistance more probable - for NNRTIs, a single mutation can do resistace – more mutations needed for protease inhibitors - treat opportunistics normally, except Pneumocystis pneumonia, Toxoplasma encephalitis and Mycobacterium avium - give prophylactics if CD4+ below 200 - most pts survive until T is at 50 - promising alternative therapy is CD4+ T cell production with IL2 – also maybe bone marrow transplants |
|
|
Parainfluenza Virus
Pathology |
- gets epi of the pharyngeal and nasal mucosa
- spread from cell to cell by fusion then spread to the epi of the larynx and trachea - resulting inflam -> croup - restriction to RT b/c host cell proteases cleave the viral fusion protein - w/out this, virions cant infect other cells |
|
|
WIN compounds (for Rhinoviruses)
|
- 108 unique serotypes -> continued re-infection
– most use same docking receptor (ICAM-1) - drugs designed to specifically bind this and prevent entry |
|
|
Rotaviruses
Diagnosis |
- detection of rotavirus (EM), or viral antigen (ELISA or PCR)
|
|
|
Human Herpesvirus 6 and 7
Treatment |
- no antiviral therapy yet
- but Ganciclovir (GCV) has been via IV to suppress HHV-6 replication in lifethreatening CNS infections in bone marrow recipients - more sensitive to GCV than ACV but GCV has more toxic side effects - no vaccine, but most newborns have maternal Ab - most infants seropositive by 13 months |
|
|
HBV structure
|
- the HBcAg is capsid protein - HBe is similar but distinct
- 3 in-frame start codons make Surface/viral envelope - L (large) M S envelope proteins - Mosly S, but most induced anti-HBs antibody is directed at epitopes in S, but can bind to all 3 - Most HBs in blood is small & spherical w/no nucleocapsid - 1st discovered “Australia ag” - not invecious, sub-unit vaccine idea - virion aka Dane particle; found at lower []s than HBs |
|
|
Polyomaviruses
BK virus |
- isolated from urine of pt after renal transplant
- in 50% of patients after bone marrow transplantation - distantly related to SV 40 |
|
|
HIV
Epidemiology |
- 750,000 and one million in US, 36 million in the world – 3rd world bad
- Worldwide spread sustained by heterosexual transmission - in US, main spread is from homosexuals and IV drugs - esp bad in coastal cities – migration to rural - leading cause of death in the US among 25 to 44 year-olds - two related variants (HIV-1 and HIV-2) - 1 is more widespread and pathogenic, 2 is mainly in western Africa - virus load is high early and late, low in between - concurrent STD infections increase risk - 15 30% vertical transmission (in utero and at birth) - AZT decreases chance - 1 in 300 in sharing needles, 90% in blood transfusions |
|
|
Parainfluenza Virus
Immunity |
- nasal secretory IgA Abs better than serum Abs
- only Abs to HN and F have been shown to neutralize virus |
|
|
HBV replicating the product from RT
|
- pdsDNA ->
- dsDNA -> (transciption) - m(+)RNA -> (RT) - pdsDNA |
|
|
Rotaviruses
Epidemiology |
- major cause of severe diarrhea everywhere
- mainly in kids under two in cooler months - first appears in the SW then sweeps NE - infection from as few as 10 virus particles - 48 hour incubation, but shed at high levels through clinical phase - subsequent infection subclinical from childhood immunity – mild if exposed to a lot - Aerosol and formite spread - resistant to inactivation - can retain infectivity for seven months at RT - frequent nosocomial infection |
|
|
Parvovirus B19
Clinical Features |
- 5th disease (age 1-5 years)
- "slapped-cheek" rash and rash on the trunk w/ low fever - adults asymptomatic or have arthralgia then flu-like - if hemolytic disorders -> transient aplastic crisis, from viral impact new erythrocyte prod, combined w/ the reduction in existing ones - can infect in utero - persistently viremic infants w/ severe anemia, so transfusions - can cause death (hydrops fetalis) |
|
|
Polyomaviruses
Structure |
- Papovavirus family
- naked, icosahedral virions - circular dsDNA - from SV40 - in 40% of tumors in non-Hodgkins lymphomas and brain and bone tumors and mesotheliomas – contaminated polio vaccine? |
|
|
HIV
Prevention Strategy/Vaccine |
- probability of STD spread determined by # of partners, likelihood that partner is infected, transmission conditions
- not all virus-containing blood has antibodies (during acute infection but prior to seroconversion) - Factor VIII and IX clotting factors are now heat treated to inactivate virus - immediate AZT treatment after exposure - No vaccine due to extreme sequence variability - must try to attain sufficiently high levels of protection to block an initial infection (since body cant rid itself of it) - most vaccines increase immunity for a subsequent infection |
|
|
HBV viral replication
|
- gapped virion DNA is completed -> to nucleus -> covalently closed circular duplex DNA (ccc DNA) that exists as a plasmid
- transcribed by host DNA dependent RNA polymerase II - Subgenomic mRNAs synthesized for protein synthesis - a genome-sized replicative RNA (pregenome) is synthesized - pregenom packaged into HBcAg - viral polymerase protein packaged (primer + RTase + RNaseH) - RT in cytoplasm occurs - This creates a nucleocapsid w/ dsDNA (and not RNA) |
|
|
Human T Cell Leukemia Virus Type I - HTLV-I
Viral Properties and Replication |
- causes adult T cell leukemia (ATL)
- envelope – one of its glycoproteins does entry into the cell – target for neutralizing Abs - carries several viral enzymes for replication |
|
|
HIV and HTLV replicating the prodcut from RT
|
- ss (+) RNA -> (via RT and RNase H)
- ds DNA -> (via DNA dep RNA pol II) -ss(+)RNA |
|
|
Rotaviruses
Treatment and Prevention |
- fluid replacement
- vaccine should prevent severe diarrhea in first 2 years (most critical) - there was a failed vaccine that was withdrawn |
|
|
Parvovirus B19
Properties of the Virus |
- typical parvovirus
- small, no enveloped icosa. - 1 molecule of +,- ssDNA - replication and assembly in the nucleus during S phase - uses host enzymes, no integration into host DNA |
|
|
Polyomaviruses
Replication |
- replicate in nucleus - do NOT encode a viral DNA dependent DNA polymerase;
- use host DNA dependent DNA polymerase for genome replication - uses host DNA dependent RNA polymerase II for transcription - progeny virions assemble in cell nucleus |
|
|
Influenza
Pandemic |
- excess mortality
- results from novel A virus - 1918, 1957 and 1968. - confined mainly to elderly and ill |
|
|
HBV clinical course
|
- 1o infections asymptomatic
- In children, mostly asymptomatic w/ high rate of chronic carriage - if immunosup, always asymptomatic and persistent - longer incubation prior to symptoms than HAV or acute HCV - Chronic may develop, CPH, CAH, PHC - staging by biopsy - CAH → cirrhosis → PHC 2-30+ years - Antigen-antibody complexes ⇒ polyarteritis, glomeru - subclinical ⇒ fatal acute fulminant - anti-HBeAbs is a good sign, along w/ viremia, less replication in liver, lesser rate of immune-mediated damage to liver |
|
|
HTLV-I
Retroviruses |
- formerly called RNA tumor viruses
- have RT and RNase H to copy RNA into DNA intermediate - integrase inserting viral DNA into the host chromosome - large precursor proteins assemble the particle then are cleaved by protease |
|
|
Pleconaril
|
- piconovirus WIN
|
|
|
Norwalk Agent
Properties and Replication |
- calicivirus, naked, (+) sense ssRNA
- fastidious in their growth requirements, replicate poorly in cell culture - humans only reservoir |
|
|
Parvovirus B19
Pathogenesis |
- narrow specificity for host cells in bone marrow, fetal liver or heart
- killing host cells (erythropoeitic cells) - causes high titer viremia w/ bone marrow depression thats short-lived, ending due to the development of Ab - rash and adult rheumatic syndrome due to immune-complex formation - infection -> lifelong immun. |
|
|
Polyomaviruses
Pathogenesis |
- only in immunosuppressed -> inapparent, cryptic infection
- transmitted via respiratory route - host cells are killed by viral cytolytic infection - cannot manifest transformation phenomenon - can be transformed to neoplastic growth in non-natural cells |
|
|
Influenza
Structure |
- pleomorphic
- smaller than paramyxoviruses - 8 segments of (-) polarity ssRNA - helical nucleocapsid w/ envelope - viral RNA polymerase is packaged within the virion - 2 proteins on surgace, hemagglutinin (H) and the neuraminidase (N) - first identifies as H1N1, but H2N2 and H3N2 also came along (so H1N1 gets younger people b/c older have immunity |
|
|
HBV Pathogenesis
|
- regulates replication level in each hepatocyte so cell isn't overstressed - no cytopathology is apparent
- replicates to very high levels in HIV pts - For HBV caused PHC, 80% of tumors have integrated HBV DNA - low level of infection at specific extra-hepatic sites - a mutant type is more fulminant and has HBe negative phenotype and serology |
|
|
HTLV-I
Clinical Features |
- low virus load w/ seroconversion shortly after infection
- malignant infected cells are mature T cells, w/ multilobed nucleus - characterized by high WBCs, infiltration of CNS and rapidly fatal course - can cause immunodeficiency, leading to opportunistic infections |
|
|
Amantadine
|
get influenza A M2 protein (to block its role as an ion channel) and prevent nucleocapsid release
|
|
|
Norwalk Agent
Pathogenesis |
- villi of the SI broaden and become blunted
- epithelial mucosa remains intact, but malabsorption -> diarrhea - nausea and vomiting due to affected gastric motor function |
|
|
Parvovirus B19
Epi |
- infected spreading virus w/in 5-6 days of infection until sufficient Abs (10-14)
- widely disseminated in community-wide epidemics via school-age children - can survive pasteurization of blood products |
|
|
Influenza A
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- in both humans and animals
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Herpesviridae family
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- herpes simplex (HSV)
- varicella zoster virus (VZV) - cytomegalovirus (CMV) - Epstein-Barr virus (EBV) - HHV 6 and HHV 7 (roseola) - HHV 8 (Kaposi sarcoma associated virus) - monkey B virus (serious neurotropic virus for humans) |
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HBV Immunity
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- specific CTLs, directed probably at HBc and/or HBe Ags
- Persistent infection can resolve, along w/ anti-HBsAbs so liver damage ends |
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HTLV-I
Pathogenesis |
- act as a cofactor in tumor formation
- first there is transient polyclonal outgrowth of cells w/ integrated DNA - inappropriate expansion may allow other genetic changes - viral expression is difficult to detect, which suggests that viral gene product is not required to maintain the transformed state and its role is early - if virus-encoded tax transcriptional activator protein increased the expression of IL2 and its receptor, cell growth would be chronically stimulated – window for genetic mutations that contribute to cell growth and malignancy - associated w/ p53 mutation and tropical spastic paraparesis (TSP), a myelopathy – SC inflame that leads to partial paralysis |
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Rimantadine
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get influenza A M2 protein (to block its role as an ion channel) and prevent nucleocapsid release
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Norwalk Agent
Clinical Manifestations and Diagnosis |
- 24 hour incubation, 24-48 hours
- nausea, vomiting (in adults), diarrhea (in kids) - no immunity if previous exposure, maybe due to different serotype or genetic # of virus receptors |
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Parvovirus B19
Diagnosis |
- clinical presentation
- isolated cases are commonly misdiagnosed as measles, etc. |
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Influenza B
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- only human, preferentially kids
- Reye's syndrome is a complication w/ aspirn - HA and NA relatively stable, genetically |
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HSV-1
Clinical Features |
- Primary Disease usually asymptomatic (esp if < 10 YO) - if symptoms, gingivostomatitis, with vesicular eruptions on mouth -> ulcerative lesions - 2-3 weeks
- latent infection in sensory neurons then reactivated disease from stress - prior to episode, often altered sensation of area, then vesicls 1-2 days later – fewer lesions than 1o and on mucocutaneous borders - asymptomatic shedding common |
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HBV primary infection
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1 - acute episode - strong immune response → clearance, recovery, no persistence, lifelong immunity (anti-HBsAb)
2 - acute episode, intermediate immune response → persistent infection → chronic liver disease 3 - no acute disease, asymptomatic → persistent infection (healthy carrier) → tolerance erodes → chronic liver disease - In healthy carriers no activated (HBV specific) CTLs. CTLs seem “anergic”. |
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HTLV-I
Treatment |
- no treatment for 1o (usually inapparent)
- chemo leads to short term remission in 50% |
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ACV acyclovir
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(analog of dG) for HSV, VZV
chain terminator |
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Norwalk Agent
Diagnosis |
- often the diagnosis in GI outbreak if others have been ruled out, more than 50% are vomiting, its an epidemic fashion, and its for 24-48 hrs
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Parvovirus B19
Treatment |
- typically not treated
- transient aplastic crisis is readily treated by blood transfusion |
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HBV epi
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- 400 million carriers, esp in
Asia, sub-Saharan, Aleuts, Am. Indians, and Polynesians - intermediate prevalence in Mediterranean countries - lower prev in western Europe and Caucasian Americans (mainly via STD) - moms can pass on so screen - teens and college at most risk - highest titer in blood, but in spit and semen |
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Influenza C
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- infects humans and swine
- causes sporadic URT illness, sometimes LRT |
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HSV-2
Clinical Features |
- Primary Disease usually symptomatic - painful, vesicular lesions on the genitals -> pustules and ulcers - systemic infection common
- reactivated Disease is milder - 1o was severe, recurrences more frequent - asymptomatic shedding common |
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HTLV-I
Epidemiology |
- via semen, milk, and blood - Male to female common, female to male rare
- Vertical (via breast feeding) is the main means - low lifetime risk if infected of developing ATL or TSP - very low level throughout the world |
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GCV ganciclovir
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(analog of dG) for CMV
chain terminator |
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Norwalk Agent
Epidemiology |
- not big in infantile diarrhea
- outbreaks in schools, institutions - gets adults and school age children - epidemics from contaminated shellfish, food, or water - 1/3 to 2/3 of GI epidemics |
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Coxsackievirus
Clinical Features |
- serogroup A and B
- can be severe in both kids and adults - may present as isolated cases or as an epidemic - infections of NS and URT, LRT, rashes, myocardial disease and conjunctivitis |
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HBV Diagnosis
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- serology
- if acute, rise in HBs Ag in acute infection then gradual decline, (immune response) - window period is when HBs Ag has disappeared, but anti-HBs Ab hasn't appeared - only sign is anti-HBc antigen - if chronic, the HBsAg rise during acute is maintained - accute can be un-noticed |
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Influenza
Replication |
- HA binds sialic acid to enter cell, then HA cleaved to uncoat – the easier it is to cleave, the more virulent
- NA cleaves sialic acid to do cell-to-cell spread - replication in nucleus - virus polymerase error prone - individual nucleocapsids encapsidate each segment, then they assemble at random into virions and bud from PM - need 8 segment, but as many as12-15 incorporated to ensure - if 2 different strains replicate -> reassortment and new combos (esp w/ A) – bad!! |
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HSV in Pregnancy
Clinical Features |
- vertical transmission of HSV-2 during delivery (asymptomatic shedding)
- recurrent disease is much less risky because of the reduced shedding of the virus - in utero cases systemic, with high mortality |
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HTLV-I
Prevention |
- Vaccination of women would work
- donated blood is screened |
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AZT azidothymidine/zidovudine
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(analog of dT) for HIV
chain terminator |
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Norwalk Agent
Treatment and Prevention |
- oral fluid replacement
- Pepto-Bismol (bismuth salicylate) to reduce symptoms - just be sanitary to prevent |
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Coxsackievirus
Serogroup A |
- herpangina - fever, sore throat, vesicles in oropharynx; acute onset
- hand foot and mouth disease w/ ulcerative vesicles on buccal mucosa, and vesicular rash on hands and feet - aseptic meningitis - typically, uneventful recovery - epidemic conjunctivitis - some forms hemorrhagic - infantile diarrhea |
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HBV vaccination
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- subunit vaccine is recombinant HBs Ag
- universal vaccination of newborns - birth, 1 month, 6 months - if job has infection risk - immediate, 1 month, 6 months - effective post-exposure if given within one week - neonates of a carrier mom immediately given HBIG and a vaccination course - exposed can get passive immun. |
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Influenza
Clinical Features |
- 3-5 day recovery, some may develop pneumonia (will be what kills you)
- asymptomatic to fatal primary influenza - clinical onset occurs with a sudden rise in temperature within 1- 4 days post-exposure - correlation b/t level shedding and severity - coughing possibly for months, as ciliated epi is re-established |
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HSV
Acute Necrotizing Encephalitis |
- most common cause, high mortality
- usually in immunocompromised |
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Human Papilloma Virus - HPV
Properties and Replication |
- naked, papovavirus family – circular dsDNA
- 70 strains w/ strict epithelial cell tropism |
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ddI dideoxyinosine/didanosine
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(analog of dA) for HIV
chain terminator |
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Adenoviruses
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- do acute respiratory syndromes and epidemic keratoconjunctivitis
- 2 serotypes (of dozens) associated with gastroenteritis - really only do nosocomial diarrhea in young children |
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Coxsackievirus
Serogroup B |
- pleurodynia - acute chest pain and fever - 2-14 days
- myocarditis and pericarditis - acute and chronic forms (due to CTL response) - neonatal infection can be inapparent to fatal - resp and CV involvement - from the nursery or transplacentally - associated with juvenile diabetes |
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HBV treatment
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- IFN for non-Asians
- Lamivudine (3TC) - Adefovir - Lamivudine + penciclovir - cant use AZT (conjugates in liver) or proteases (doesn't encode protease) |
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Influenza
Pathogenesis |
- gets cells lining the air passages
- replication -> desquamation of ciliated epi - if 2o bacterial infections, harder to clear it -> bacterial pneumonias from step, staph, and Haemophilus - 1o viral pneumonia is less common, usually old or CP disease -> hypoxema and death - Reye’s syndrome (cerebral edema / degen of liver) in kids w/ B |
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Herpes simplex Keratoconjunctivitis
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- second to trauma as a cause of corneal blindness in the U.S.
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Human Papilloma Virus - HPV
Clinical Features and Pathogenesis |
- cause epithelial dysplasias (i.e., warts)
- via viral contact with MMs or traumatized skin - some cause common warts, others associated w/ carcinomas - in the cancers the viral genome is frequently integrated breaking the circular DNA so that an important viral regulatory protein is not produced -> viral genes E6 and E7 to be produced at a higher level -> inactivating the cell’s tumor repressor genes, Rb and p53 |
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3TC lamivudine
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(analog of dC) for HIV, HBV
chain terminator |
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Coxsackievirus
Properties of Virus |
- typical enteroviruses
- naked, icosahedral - 1 molecule of (+) RNA - replication confined to the cytoplasm like polioviruses |
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Adefovir
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- treats HBV
- acyclic nucleotide similar to dAMP - ring more flexible - converted first to mono then to di-phosphate which is dATP analog - terminates chain of HBV DNA synthesis |
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Influenza
Epidemiology |
- great unconquered epidemic
- person to person via droplets - Antigenic Drift - high mutation rate (since RNA) - HA Ab correlated with protection against disease so changes in HA protein -> new strains that can escape neutralizing Ab - antigenically new strains every 2-3 years - Antigenic Shift – (1) in A zoonotic allows reservoirs for propagation of viruses, more H and N possibilities – (2) individual cells may be infected w/ different virus strains – (3) segmented nature of genome |
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HSV
Structure |
- large dsDNA
- icosahedral capsid surrounded by the tegument in envelope |
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Human Papilloma Virus - HPV
Diagnosis |
- find cervical dysplasia in paps
- PCR to identify a specific strain |
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Adefovir
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- (analog of dAMP) for HIV, HBV
- undergoes two sequential (P) rxn by host kinases to produce the active drug, adefovir diphosphate (analog of dATP) |
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Coxsackievirus
pathogenesis |
replicates in OP and GI lymphoid tissue ⇒ the RES ⇒ skin, myocardium and the central nervous system
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Influenza
Treatment |
- Supportive treatment for relief - acetaminophen for aspirin reduces risk of Reye’s syndrome from B
- amantadine (rimantadine) Anti-Viral Drug - inhibits of uncoating – gets A if given w/in 28 hrs – shortens course - Neuraminidase Inhibitors (A and B) - binds sialic acid on NA - Prevent w/ prophylactic amantadine (for A only) |
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HSV
Replication |
- in nucleus
- transcription by host DNA dependent RNA polymerase II - replication by virus-coded DNA dependent DNA polymerase - envelope and maturation in cytoplasm |
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Lamivudine
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- 3TC, treats HBV
- blocks viremia, but most cases rebound in post-drug setting - long term benefit uncertain |
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Human Papilloma Virus - HPV
Epidemiology |
- via direct contact - more common in older children and young adults
- not highly contagious, epidemics are rare, but genital warts #1 STD (w/ Chlamydia) - 2-6 month incubation - cervical cancer is 1/4 of all cancer in women - some genital tract HPVs (including the squamous cell cervix carcinoma one) are considered STDs – high # of sexual partners is main RF |
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Pyrophosphate analog
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- For HSV, CMV, HIV
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Coxsackievirus
Epi |
- fecal-oral mainly, but also
inhalation of droplets - active infection may block poliovirus vaccine - concurrent enterovirus infections can interfere with replication among each other; one enterovirus infection then dominates |
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Influenza
Vaccines |
- Currently formaldehyde-inactivated virions from embryonated eggs - 2 doses (1month interval) - induces anti-HA Ab in 85% - immunity short lived
- one dose for adults, 2 for non-immunized kids (4 wk interval) - WHO network monitors and detects new viruses - vaccinate old, infants, chronic disorders, and pregnant - Trivalent vaccine for 2004 - 2005 - FluMist™ - cold-adapted, live-attenuated, trivalent - Molecular vaccines - appropriate HA Ags in genetically engineered bacteria and live attenuated A and B chimeric viruses |
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HSV
Pathogenesis |
- invades epi -> multinucleate giant cells
- released via exocytosis and cell necrosis - main pathogenic effect is cell lysis - leaks vesicular fluid between the dermis and epidermis creating the vesicle |
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Lamivudine and penciclovir
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- chain-terminators, treat HBV
- used in liver transplant pts - drug-resistant strains emerge due to mutations in HBV RT |
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Human Papilloma Virus - HPV
Prevention and Treatment |
- Limiting # of sexual contacts and do regular Paps
- 50% of common skin warts will regress spontaneously - can do surgical removal, but reoccurrence is common |
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Neviparine
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for HIV - binds directly to HIV RT and inhibits the DNA poly
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Coxsackievirus
Diagnosis and Treatment |
- can be isolated from stool samples, pharyngeal secretions and vesicular fluids
- serum typed for presence of convalescent antibodies - no antiviral drugs or vaccines available |
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HSV
Epi |
- HSV-1 universal, usually before 5
- spread by direct contact with lesions or secretions - asymptomatic kids are major HSV-1 source - no animal vectors or seasonal patterns - sex is HSV-2 source – 20% of females shed asymptomatically |
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HDV genome
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- small, circular ssRNA virus
- no genes for envelope or replicating - replicates only in host cells HBV co-infected - 1 ORF for HD Ag (internal core protein) - (-) sense, so unique b/c it does NOT encode RNA-dependent RNA-polymerase - uses host DNA dependent RNA polymerase II |
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Epstein Barr Virus
Properties and Replication |
- herpesvirus that gets 90% of the world pop
- linked to B-cell and epithelial malignancies - can infect B’s in vitro and induce growth in culture - most cell lines from PBL don’t produce infectious virus – considered “latently” infected - In nucleus, linear DNA forms the extrachromosomal episome - replicated by host and partitioned to each daughter cell (as long as oriP and EBNA1 are there) |
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Ribavirin
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(analog of rG) for RSV, Lassa, HCV – (P) then inhibits rxn w/ rGTP – also act as an immunomodulator
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HSV
Diagnosis |
- history and vesicular lesions
- characteristic CPE in tissue culture - in herpes encephalitis, PCR of the CSF |
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HDV structure
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- RNA formed into a fragile nucleocapsid with the HD Ag
- parasitizes envelope form HBV lipoprotein - The viral RNA is also a ribozyme - can self cleave, and ligate |
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Epstein Barr Virus
Clinical Features and Pathogenesis |
- 1o usually early in life, frequently by age 3
- largely asymptomatic - IM, BL, NPC, HD |
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IFNs (alpha, beta and gamma)
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- cytokines in response to infected cell or RNA
- bind to specific receptors on target cells and induce 'responses' and transcription – some block RNA and protein synthesis, and others step in the infection process – for HCV and papilloma viruses |
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HSV
Treatment |
- no vaccine for either form is yet licensed
- acyclovir (Zovirex™), a nucleoside analog – only active in virus-infected cells -> chain termination - can become resistant from mutations of viral TK that don’t accept ACV - fortunately, acyclovir resistant mutants are avirulent - a new subunit vaccine of HSV-2 envelope D is in trial |
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HDV clinical features
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if co-infection with HBV, there is a more aggressive clinical course with higher mortality
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EBV
Infectious Mononucleosis (IM) |
- salivary exchange, then replicates in epi (tonsillar lymphocytes?) -> viremia
- 1st wk - portion of circulating Bs are EBNA (+) and may produce IG and autoantibodies (the heterophile Ab reacts w/ sheeps blood and is used to diagnose) - imbalance between a polyclonal proliferating and latently-infected B’s VS cytotoxic T’s that would control them - then there is latent infection in B’s (escapes the cytotoxic Ts) - virus DNA persists as episome and infection persists for life - degree shedding varies – may reflect a chronic low grade replication in OP epi cells |
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Negri bodies
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Rabies virus
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HDV pathogenesis
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- Two infection settings
1) Naive pts get both HBV and HDV simultaneously -> acute episodes of both, first HBV, then HDV -> high, transient viremia 2) HBV carrier gets HDV as a superinfection -> chronic forms of both |
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EBV
Burkitt’s Lymphoma (BL) |
- endemic area in Africa, tumors in jaw - kids before two years
- characteristic chromosomal translocation that alters the regulation of c-myc expression so its controlled by IG promoters - elevated Ab titers to viral Ags, like VCA and EA, preceding the tumor - All tumors have EBV in all of the malignant cells |
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Indinavir, Saquinavir, Ritonavir
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Protease inhibitors for HIV
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HDV immune response
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- Acute vs chronic is determined by immune response to HBV
- If the immune system clears HBV from the liver, it also clears HDV |
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EBV
Nasopharyngeal carcinoma (NPC) |
- epithelial tumor - in Asia - elevated Ab titers to viral Ags
- viral genome in malignant cells - other co-factors contribute to cancer development - latent infection then expression of viraltransforming genes are crucial events |
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Zanamivir (Relenza)
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- Inhibitors of the Influenza A and B
- analog of sialic acid |
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HDV Epi
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- Transmission probably like HBV
- In the US, outbreaks in IV drug users who share needles |
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EBV
Hodgkin’s disease (HD) |
- if history if IM, 2 to 4X more likely to get this lymphoma which develops from EBV infected cells
- Reed-Sternberg cell (similar to those in IM) is malignant cell - viral DNA and EBERs commonly found in RS cells |
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Guarnieri bodies (cytoplasmic)
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smallpox virus
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HDV diagnosis
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- Detect either HD antigen or antibody to HD antigen
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EBV
Lymphoma associated with immunosuppression |
- may develop in patients with congenital immune impairment
- also responsible for most post-transplant lymphoma (PTL) |
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Nuclear and Cytoplasmic inclusions
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measles virus
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HDV treatment
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- No specific treatment or vaccination
- Vaccination for HBV protects against HDV - Lamivudine or penciclovir will inhibit HBV RT process, but NOT synthesis of HBs Ag - so they wont affect the course of HDV infection |
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EBV
Diagnosis |
- IM is characterized mononucleosis (atypical lymphocytosis) and “monospot” test (sheep blood thing)
- malignancies identified clinically in high risk populations - BL or NPC have serologic responses prior to onset of malignancy |
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EBV
Treatment and Prevention |
- latent infections, so antiviral therapy for the viral DNA polys wont work
- IM self-limiting, symptoms vary widely - no vaccine (it would eliminate ass. Cancers) - Post-transplant lymphoma treated by reducing immunosuppression and by giving viral-specific cytotoxic lymphocytes - in cancers, multiple viral proteins for weird growth so immune-mediated therapy and specific molecular therapy directed toward the viral functions will work |
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Human Herpes Virus 8 (HHV-8)
Virus Properties and Replication |
- most recently discovered HHV, discovered in Kaposi’s sarcoma (KS)
- in transformed cell, viral DNA is circular, possibly clonal - has genes acquired from the host genome - may induce growth by inducing infiltrating cells to secrete cytokines or by expressing autocrine growth stimulatory molecules |
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Human Herpes Virus 8 (HHV-8)
Clinical Features and Pathogenesis |
- KS not very aggressive - forms multiple skin lesions
- incidence has dramatically increased in HIV patients - caused by a STD agent, with patterns of appearance, remission, reactivation seen in other herpesviruses |
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Human Herpes Virus 8 (HHV-8)
Epidemiology |
- consistently detected in AIDS-associated as well as classical KS
- rarely detected in normal healthy subjects - sometimes in AIDS lymphomas - may not be ubiquitous |
