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56 Cards in this Set

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What are the 3 classes of mRNA in Herpes viruses?
alpha polypeptides - function not clear, may be related to latency

beta polypeptides - virus specific thymidine kinase and DNA polymerase (important targets for development of antivirals). Synthesis of beta polypeptides shuts off synthesis of alpha polypeptides and initiates synthesis of gamma polypeptides

Gamma polypeptides - structural components of virus particle
Herpes virus stucture
dsDNA
Enveloped - buds through nuclear membrane
Linear genome, which becomes circular during latency state
Where is the site of Herpes simplex 1 latent infection?
Trigeminal nerve root ganglion
Herpetic whitlow
Cause by HSV-1 and HSV-2
Clinical manifestations of herpes simplex viruses
Herpetic whitlow - Infection of finger or nail. Result of inoculation of cut, abrasion with secretions - often from patient's own saliva. Painful vesiculating, pustular lesions.

Corneal and conjunctival infections - may lead to conjuctival scarring and blindness. Characterized by distinct dendritic ulcerations: pathognomonic. DO NOT GIVE TOPIC STEROIDS

Encephalitis - up to 10% of all cases of viral encephalitis. Devastating illness - mortality untreated about 70%, survivors often have extensive neurologic deficits. Intravenous acyclovir decreases mortality.
What are the rates of recurrent genital herpes?
80% of primary infections lead to latency and recurrence

Median recurrence rate is 4-5 episodes per year
Neonatal herpes
Usually results from contact with infected genital secretions of mother during delivery.

Lack of normal immune response in neonate leads to devastating, disseminated disease: overall mortality rate of 60%, high rate of neurologic sequelae in survivors.
Cytomegalovirus
dsDNA
Enveloped

Isolated from saliva, cervical secretions, semen, urine, and white blood cells (specifically neutrophils)

Infects epithelial cells ("owl's eye effect") and leukocytes

Congenital infection is really bad
Congenital CMV infection during pregnancy
Most infants appear normal

20% develop sensory nerve hearing loss, psychomotor mental handicap, or both

Almost all infants with congenital infection are born to mothers who experience primary infection pregnancy
Epstein-Barr virus
dsDNA
Enveloped

Can be isolated only from lymphoblastoid cell lines derived from human B cells

Does not produce cytopathic effect

No vaccine
What antibody is diagnostic of acute infectious mononucleosis?

What about chronic?
Acute: IgM anti-VCA (viral capsid antigen)

Chronic: anti-EBNA (nuclear antigens)
Which malignancies are associated with Epstein-Barr virus?
African Burkitt's lymphoma

Anaplastic nasopharyngeal carcinoma

B-cell lymphomas
Which cells does Epstein-Barr virus infect and through which receptor?
Cell - B cells

Receptor - C3d (complement) receptor
What are heterophile antibodies?
Unrelated antibodies of IgM class which respond with all kinds of crazy antigens

Probably due to polyclonal activation of B cell by Epstein-Barr virus
What are the laboratory diagnoses for Epstein-Barr virus infection?
Detection of heterophile antibodies and detection of specific pattern of anti-EBV antibodies
What percentage of the mammalian genome is made up of endogenous retroviruses?
10%
What are the human retroviruses?
HIV
human T-cell leukemia virus type 1 and 2 (HTLV-1 and HTLV-2)
Tat gene (HIV)
Major transcriptional transactivator of HIV-1 and essential for the activity of the LTR promoter. The Tat protein stimulates HIV-1 transcription via an RNA intermediate called the TAR region, which is found just downstream of the 5'LTR.
Rev gene (HIV)
Rescues the unspliced viral RNA from the nucleus of infected-cells by increasing transport through the nuclear pore.
Vpu gene (HIV)
Stimulates viral release.
Vif gene (HIV)
Prevents hypermutation of viral genome by cellular deaminase APOBEC3G.
Human Papillomavirus (HPV)
dsDNA
Non-enveloped
Small
Transformation ability

Virions only produced in cornified epithelium

HPV types 6 and 11 - associated most frequently with benign genital warts in males and females; associated with some instances of cervical dysplasia in females; lesions only rarely become malignant.

HPV types 16, 18, and 31 - Cause warty lesions of vulva, cervix, penis, and anus; more often progress to malignancy
What changes are seen in cells infected with HPV?
Perinuclear cytoplasmic vacuolization, nuclear enlargement, and other changes in epithelial cells of the cervix and vagina.

Seen in pap smears
What strains of HPV does Gardasil create immunity for?
Types 16, 18, 6, and 11
JC virus
dsDNA
Non-enveloped
Small
Transformation ability

Diagnosis - urine from patients excreting polymoa viruses may contain cells similar to those found in patients excreting CMV; Immunoassays can also demonstrate viral antigens.

Diseases caused : Progressive Multifocal Leukencephalopathy (PML) and urinary tract infection
Progressive Multifocal Leukoencephalopathy (PML)
Associated with JC virus

Virus reactivates in immunocompromised individuals (i.e. AIDS). Causes subacute, degenerative disease of the brain.

Symptoms:
- Impaired memory, confusion, and disorientation initially
- Followed by hemiparesis, visual disturbances, incoordination, and seizures
- Progressive; death occurs 3 - 6 months after onset of symptoms

CSF testing often normal; foci of demyelination due to damage to oligodendroglial cells; JC virus particles visible by EM

No treatment, except reduction in immunosuppression if possible
BK virus
dsDNA
Non-enveloped
Small
Transforming ability

Causes urinary tract infections and hemorrhagic cystitis in bone-marrow transplant patients

BKV can be readily isolated in fibroblasts and other cells
Rabies virus
ssRNA
Enveloped
Bullet-shaped

Virus enters unmyelinated peripheral nerves, possibly by attachment to Ach receptor; virus travels to CNS (replication and assembly of mature virions); Virus migrates from CNS through nerve terminals of organs, especially salivary glands

Incubation period:
Typical - 4 to 6 weeks
Range - 7 to 10 days to 7 to 8 years
Rabies vaccine and immune globulin
Vaccine - human diploid cell vaccine commonly employed in USA; active induction of virus neutralizing antibody in 7 to 10 days; IM administration most common

Rabies immune globulin - rapid, passive viral neutralization (but short duration); HRIG - human origin, prepared from pooled rabies-immune donor sera
Clinical manifestations of hepatitis A virus
Incubation period 14-40 days (mean 25 days)

Liver enlarged and tender; abnormal liver function tests

Chronic HAV rare or non-existant; fulminant, fatal hepatitis associated with extensive liver necrosis can occur

Immune serum globulin (ISG) - 80-90% effective

Vaccine - administered as 2 doses, recommended for all infants 1 year of age
Hepatitis B virus replication cycle
Involves reverse transcription step, unique to DNA viruses.

One strand, short strand of variable length, is associated with viral DNA polymerase and is positive-sense.

Other strand, long strand, is completely and of negative-sense.

Full length viral positive sense RNA transcripts are inserted into maturing core particles; these mRNAs serve as templates for reverse transcriptase that synthesizes a full length negative sense DNA strand.

Positive sense DNA strand is initiated but not completed prior to virus maturation and release.
Hepatocellular carcinoma is strongly associated with what virus?
Hepatitis B virus
What symptom of HBV is not typical of HAV?
Rash or joint pain
Hepatitis B prevention
Hepatitis B immune globulin - emergency measure

Vaccine - recombinant vaccines; immunization requires 3 doses

Infants born to infected mothers require a combination of passive and active immunization

Active immunization recommended for all infants (first dose on day of birth)
Hepatitis B treatment
No good treatment

Some use for interferon, some use for lamivudine (reverse-transcription inhibitor)
Hepatitis D
ssRNA
Small
Requires presence of HBsAg for transmission but not replication

Causes rapid progression of disease already present with HBV
Hepatitis C
ssRNA, actually a flavivirus

Chronic carrier state is common - 70% of those infected

Transmitted by blood

Greatly increased risk for liver cancer; one of the 3 most common reasons for liver transplantation

Tx - best results w/ pegylated INF-alpha and ribavirin
Clinical disease manifestations and outcomes for polio
Abortive poliomyelitis - nonspecific febrile illness, 3 - 5 days duration, no signs of CNS involvement.

Aseptic meningitis - non paralytic poliomyelitis; signs of mental irritation (stiff neck, pain & stiffness in back), no permanent effect.

Paralytic poliomyelitis - asymmetic flaccid paralysis, no significant sensory loss. Extent of nerve involvement varies: all four limbs may be involved, or brain stem may be involved - leading to respiratory problems.
What are the 2 types of polio vaccine?
Inactived polio vaccine - "Salk" vaccine

Oral polio vaccine - live, attenuated vaccine; "Sabian" vaccine

Recent recommendation in USA: 2 doses of IPV, followed by 2 doses of OPV
Most common manifestations of coxsackieviruses and echoviruses
Aseptic meningitis - usually mild and self-limited, often characterized by sufferers as "the worst headache you've ever had in your life." Encephalitis is possible, but rare.

Rashes - usually in children. Best example is hand-foot-and-mount disease; frequently associated with coxsackievirus A16 and enterovirus 71.

Acute inflammation of the heart muscle (myocarditis); group B coxsackieviruses are the most frequently implicated.
Rhinoviruses
(+) ssRNA
Optimum temperature is 33 degrees C
Incubation period 2-3 days
Duration of acute symptoms about 3-7 days

Frequent causes of the "common cold"
Epidemic peaks in early fall or spring

No vaccines, no specific therapy
Rotavirus
dsRNA, 11 segments, no envelope, but 3 concentric capsids

1-3 day incubation period

Abrupt onset of vomiting, followed quickly by watery, brown, copious stools; stools may become clear; low-grade fever often present.

Vomiting: 1-3 days
Diarrhea: 5-8 days

Vaccine - first one caused intussusception (Rotashield); RotaTeq now routine vaccination of US infants

By age 4, 90% of children have serum antibodies
Norwalk viruses
ssRNA, non-enveloped, small

Brief illness - 1-2 days
Similar symptoms to Rotavirus

Protective effect of antibodies appears minimal; reinfection/illness with same serotype occurs repeatedly

Common source of outbreaks associated with water - uncooked shellfish

No vaccine available; by 5th decade of life, 50% of people have antibodies
What are the laboratory tests for Rotavirus?
ELISA assay to detect virus Ag in stool specimens
What is the immune response to Rotavirus?
Type specific serum (IgG) and secretory antibodies (IgA) - long lasting, probably protective

Breast feeding seems protective (probably via transfer of maternal IgA)
Enquine Encephalitides
(+) ssRNA
Buds through host cell membrane

All mosquito transmitted

Natural reservoir of these diseases is birds and small animals

Incubation period 4 to 21 days; sudden onset of severe headache, chills, fever, nausea, vomiting, generalized pain, and malaise.

Within 24 to 48 hours, marked drowsiness, stupor may occur (invasion of CNS); nucchal rigidity common. Mental confusion, tremors, convulsions, coma may develop in severe cases. Fever lasts 4 to 10 days.

Sequelae: mental deterioration, personality changes, paralysis, aphasia, and cerebellar signs.

No immunzation available
St. Louis Encephalitis (SLE)
(+) ssRNA

Mosquito is vector

Similar to equine encephalitides
Japanese B Encephalitis
Endemic to Japan and China

Vector is mosquito, swine are important reservoir host
Yellow Fever
(+) ssRNA

Initial multiplication of virus in regional lymph nodes; viremia and dissemination to liver, spleen, kidney, bone marrow, and other lymph nodes.

Secondary multiplication of virus, cellular destruction. Destruction of liver cells leads to jaundice. Death may occur from necrosis of liver or kidney.

Clinical findings: incubation period 3 to 6 days. Fever, chills, headache, backache, nausea, and vomiting. Short period of remission.

Day 4, serious symptoms develop: slow pulse, jaundice, hemorrhagic phenomena, signs of kidney damage.

Live attenuated vaccine available
Dengue (Breakbone Fever)
(+) ssRNA

In most respects similar to Yellow Fever, except site of virus is in small blood vessels, not regional lymph nodes

Clinical findings: Fever, possibly after prodrome of malaise, chills, and headache. Pains soon develop in back, joints, muscles, and eyeballs. Temperature returns to normal, may rise again ("saddleback" fever curve). Rash may develop on 3rd or 4th day (secondary viremia), lasts 1 to 3 days, disappears with desquamation. Convalescence may take weeks.

Death is rare

Variant: Denge hemorrhagic fever

No vaccine
Dengue hemorrhagic fever
Occurs in individuals with passively acquired maternal antibody or in those repeatedly infected with heterologous strains of dengue virus; an immune phenomenon.

Initial course resembles normal dengue infection. Manifestations of coagulation abnormalities appear (shock, bleeding). Caused by plasma leakage through damaged endothelial cells; shock is hypovolemic.
California encephalitis
(-) ssRNA
Enveloped
Buds on Golgi apparatus

Clinical findings: Abrupt onset, typically with severe bifrontal headache, fever of 38-40 C, sometimes vomiting or lethargy or convulsions. Prognosis good, though convalescence may be prolonged.

Natural hosts probably small woodland mammals
Lassa Fever
(-)ssRNA
Enveloped
Double-segmented

Probably transmitted by contact with rodent urine

High fever, mouth ulcers, severe muscle aches, skin rash with hemorrhages, pneumonia, heart and kidney damage.

Often fatal when contracted as an adult

Ribavirin is reportedly effective in Tx
Lymphocytic Choriomeningitis Virus
(-)ssRNA
Enveloped
Double-segmented

Presents as either aseptic meningitis or as mild flu-like illness.

Probably transmitted by contact with or inhalation of mouse droppings and urine

No specific therapy

Transplacental transmission - for God's sake stay away from hamsters
Marbug virus
(-) ssRNA

Hemorrhagic fever - bleeding from mucosa, shock, and virus is located in all body secretions
Ebola virus
(-) ssRNA

Hemorrhagic fever - bleeding from mucosa, shock, and virus is located in all body secretions