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104 Cards in this Set
- Front
- Back
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What is the treatment for HSV?
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3 nucleoside analogs (guanosine analogs)
- acyclovir - famciclovir -valacylovir They are chain terminators since they are missing 2' and 3' OH |
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What is the latency depot for HSV 1 to 8?
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HSV 1,2 - sensory neurons
HSV 3 - sensory neurons HSV 4 - lymphoid tissues HSV 5 - multiple tissues HSV 6 - lymphoid tissues HSV 7 - lymphoid tissues HSV 8 - lymphoid tissues |
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Which hepatitis virus(es) cause only acute infection?
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HAV
HEV |
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Hepatitis A virus:
name the virus family and its transmission route |
picornavirus (+ssRNA)
fecal/oral |
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Hepatitis B virus:
family name and transmission route? |
Hepadnavirus (partially dsDNA)
blood/sex |
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What is the treatment for HBV?
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interferon/peginterferon
HIV drugs (target reverse transcriptase) nucleoside analog |
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What are HBV's gene transcripts
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S = surface antigen (and pre-S1, pre-S2)
P = reverse transcriptase C = core (and pre-C) X = ??? |
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Hepatitis C virus:
family name and transmission route? |
Flavivirus (+ssRNA)
Blood |
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What percent of acute HCV infections become chronic?
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80-90% become chronic
~20% clear the acute infection |
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What is the treatment for HCV?
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ribavirin, IFN-alpha, peginterferon
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Why are there no vaccines for HCV?
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HCV elicits weak immune response
No cell culture system to grow HCV or non-primate models Variable isolates due to nucleotide and protein mutations |
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Hepatitis D virus:
family name and transmission route? |
Viroid-like (-ssRNA)
Blood |
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What's so special about HDV and what protein(s) does it encode?
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HDV needs help of HBV to infect host.
HDV only encodes delta-antigen which binds genome HDV replicates by "rolling circle" FYI |
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Hepatitis E virus:
family name and transmission route? |
Caliciviridae (+ssRNA)
Fecal/oral (fecally contaminated water) |
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Henipaviruses are part of which family? and name the 3 henipaviruses
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Paramyxo family
Hendra, Nipah, Cedar |
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What are the proteins of henipaviruses
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2 surface proteins: F, G
M matrix protein N,P,L = transcriptase complex |
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How are hendra viruses transmitted?
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Fox headed fruit bat's --> horse --> human
(Australia) |
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How are Nipah viruses transmitted?
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Fruit bats lick pots that collect tree sap --> human
(Malaysia) |
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What do Hendra viruses cause in humans?
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renal failure
respiratory disease |
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What do Nipah viruses cause in humans?
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Encephalitis
respiratory disease 1/4 get seizures 60% comatose |
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Henipavirus genome contains 6 cistrons. What do the intergenic regions do
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Cause pausing and attenuation of polymerase
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What is SSPE? (subacute sclerosing panencephalitis) Which virus cause this and how?
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rare chronic progressive encephalitis in children/young adults
caused by persistent measle virus (paramyxoviridae) virus is defective: it doesn't produce M protein thus cannot bud out of host cell, so the virus constantly evokes immune response causing SSPE |
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Does nipah or hendra virus cause more relapse?
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nipah
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How do you get Castleman's disease? What are the types of Castleman
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You need to be infected with 3 viruses: HHV8, HIV, HBV
Unicentric Castleman: slow growing, solitary. Can be cured with surgical resection. Not associated with other tumors Multicentric Castleman: acute disease, may die in a week. Fever, splenomegaly, hepatomegaly, diffuse lymphadenopathy, edema, respiratory |
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What diseases does HHV 8 cause? (4)
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Kaposi Sarcoma
Castleman's disease PEL (primary effusion lymphoma) Extracavity PEL |
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Primary CNS lymphoma is seen in what kind of people? What does it cause? How can it be cured?
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advanced HIV patients (who have CD4 < 50)
cerebral nodules cure with ART (antiretroviral therapy) |
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What are the two main viruses that cause viral diarrhea (viral gastroenteritis)?
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Rotavirus (Reoviridae)
Norovirus (Caliciviridae) |
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Name 4 viruses, 4 bacteria and 3 parasites that cause gastroenteritis
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Viruses
- rotavirus - norovirus (calicivirus) - adenovirus - astrovirus Bacteria: salmonella, shigella, cholera, E.coli Parasites: Gardia lamblia, Entamoeba histolytica, Cryptosporidium |
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What are the 2 triggers for gastroenteritis?
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Inflammation from direct invasion of gut wall
Toxins causing loss of water and electrolytes |
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Which gastroenteritis virus infect children 3-15 months old?
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Rotavirus
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Which gastroenteritis virus infect children under 2?
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Adenovirus
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Which gastroenteritis virus infect all ages and are the most common cause of viral gastro leading to epidemics?
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Calicivirus
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Which gastroenteritis virus infect children and elderly?
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Astrovirus
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What type of genome does rotavirus have?
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10 segments of dsRNA
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Describe rotavirus' triple-layer structure
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Outer layer - VP 4,7 - derived from ER membrane
Outer shell - VP6 (260 trimers) Inner shell - VP2 (60 dimers), VP1(RdRp), VP3(capping enzyme) 132 aqueous channels span VP7 and VP6 VP6 and VP2 form a channel for mRNA to exit |
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Describe the entry of Rotavirus
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VP4 is cleaved to VP5 and VP8
-VP5 binds sialic acid -VP8 binds integrins Outer layer is lost upon entry of host cell (double layer particle enters cell) |
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How do rotaviruses exit host cell
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Lyse cell (it does not bud out to get host derived envelope!)
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How many subtypes of rotaviruses are there? Which cause most of the infections?
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7 subtypes: A to G
A causes 90% of infections |
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What is the transmission route and tropism of rotavirus?
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Oral/fecal route
Infect intestinal enterocytes |
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What is the treatment for rotavirus infection? prevention?
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treatment: oral rehydration
prevention: Rotarix (GSK) and RotaTeq (Merck) vaccines |
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Which dsRNA segment of rotavirus causes diarrhea?
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Segment 10 = NSP4 = enterotoxin
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What type of genome does norovirus (caliciviridae) have?
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+ ssRNA
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Describe the grouping system of norovirus
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5 genogroups (GI-V) - shares 51-56% nucleotide similarity
Each genogroup is divided to genotypes: GI has 8 genotypes: GI.1 = Norwalk (prototype.. first virus isolated that causes diarrhea) GII has 17 genotypes |
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Which genogroup and genotype of norovirus that accounts for 70-80% of norovirus outbreaks?
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GII.4
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Which virus is the most common viral gastroenteritis?
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norovirus (caliciviridae)
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What are the features of norovirus ?
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highly contagious
viral shedding precedes illness and after illness hardy - survives range of temperature gives sudden onset of vomiting / diarrhea great diversity - easily get mutations major genotype to cause epidemics vary each year |
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Why is it difficult to make a vaccine for norovirus infection?
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major genotype to cause epidemics vary each year
great diversity - easily get mutations binds to diverse binding sites lack of reliable cell culture system and animal models |
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Which receptor does norovirus bind to?
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HBGA (histo-blood group antigens) which are found on RBC, gut, respiratory epithelials, human secretions
3 groups of HBGA: ABO, Lewis, Secretor families |
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Name the surface proteins of norovirus
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P1
P2 S |
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Describe host resistance to norovirus infection
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Host polymorphism of HBGA
20% of Europeans are non-secretors no functional fucosyltransferase 2 gene |
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What are the 4 factors for susceptibility and severeness of viral respiratory diseases?
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Genetic factor (immune system)
Immune factor (immunosuppressed) Viral factor (virulence) Physical factor (small airway) |
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How do you diagnose viral respiratory diseases?
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virus culture
RT-PCR serology antigen detection |
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What are the two types of symptoms of viral respiratory diseases?
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URTI: congestion, hoarse, cough, rhinitis, pharyngitis, fever
LRTI: wheeze, tachypnea, severe cough, breathless |
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List viruses that cause viral respiratory diseases
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Respiratory syncytial virus (RSV), Rhinovirus, Reovirus, Adenovirus, Coronavirus, Influenza, Parainfluenza, Enterovirus, Human metapneumovirus, Bocavirus, Poluomavirus
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What family is rhinovirus from? Describe its size, genome and structure. How many serotypes are there?
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Picornaviridae
+ ssRNA non-enveloped, 30nm 99 serotypes |
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Which receptors does rhinovirus bind? What's its tropism?
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ICAM-1 (major), LDL-R (minor)
Respiratory epithelium, local infection |
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Which age group is targeted by rhinovirus?
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ALL ages
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Which virus causes half of the common cold?
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Rhinovirus
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What are the treatments and vaccines for rhinovirus infection?
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none
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Which virus causes 10-30% of common colds?
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Coronavirus
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Describe size, structure and genome of coronavirus
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enveloped, 80-200nm
+ ssRNA |
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What is the tropism of coronavirus?
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upper respiratory tract
gastrointestinal tract |
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What ratio of coronavirus infections is asymptomatic?
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1/2
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Which virus has 50+ serotypes, causes 3-5% of respiratory infections in children and 2% in adults, and causes many diseaes
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Adenovirus
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What diseases does adenovirus cause
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respiratory illness
gastroenteritis Reye's syndrome hepatitis |
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Describe size, structure and genome of adenoviruses
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linear dsDNA
non-enveloped 80-100nm |
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Which virus is not associated with any human respiratory diseases?
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Reovirus (respiratory enteric orphan)
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Describe size, structure and genome of reovirus
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65-70nm
non-enveloped 10 segments of dsRNA |
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Describe size, structure and genome of parainfluenza. What family does this virus come from
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150-200nm
Enveloped, pleimorphic (-)ssRNA (linear) Paramyxoviridae |
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Which virus causes 75% of croups?
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Parainfluenza
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Describe family, structure and genome of respiratory syncitial virus
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Paramyxoviridae
enveloped, pleimorphic (-)ssRNA |
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Which group of humans does RSV target? What is its transmission route and tissue tropism?
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Infants, elderly, immunocompromised
Aerosol/direct contact Nasopharynx - superficial cells of respiratory epithelium |
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What are the infection features of RSV?
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highly infectious
less invasive and pathogenic than influenza one serotype: limited antigenic and strain diversity early life infections (peak at 2 months old infants) can get reinfections |
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Even though there is only 1 serotype of RSV (limited antigenic/strain diversity), why do we still get reinfections?
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G protein is heavily glycosylated
Secreted G proteins neutralize antibodies Tissue tropism (superficial cells) reduce immunity's effectiveness Immunologic immaturity (infants) |
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How does RVS's tissue tropism reduce the immunity's effectiveness at clearing the infection?
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local IgA response is shortlived
CD8 cytotoxic T cells are impaired when in lungs Difficult for serum antibodies to reach respiratory lumen Delayed antigen presentation of RSV antigen to immune system |
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Describe structural and non-structural proteins of RSV
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3 surface proteins: G, F, SH(??)
Transcriptase complex: N, P, L NS proteins shut down innate immunity NS2 inhibit RIG-I, MDA5, NFkB |
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Which receptors does RSV bind to?
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Heparin
Proteoglycan |
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Describe the pathway of how a cell detects RSV and produce antiviral proteins
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RIG-I and MDA-5 detect RSV in cytoplasm
RIG-I and MDA-5 activate transcription of IFN IFN-alpha/beta activates STAT pathway STAT pathway activate transcription of ISG genes ISG= IFN stimulated genes => antiviral proteins |
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How does the cell detect RSV on the surface, in cytoplasm and in endosomes?
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Surface: TLR2/6, TLR4
Cytoplasm: MDA-5, RIG-I, NLRP Endosome: TLR3, TLR7 |
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How does RSV evade detection?
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NS2 inhibits RIG-I, MDA5, IRF3, NFkB, JAKSTAT
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Which are the major types of influenza causing annual human epidemics?
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influenza A and B
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Describe genome of influenza
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Influenza A,B: 8 strands of (-)ssRNA
Influenza C: 7 strands of (-)ssRNA |
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List structural and non-structural proteins of influenza
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HA, NA
M1 (matrix protein), M2(ion channel) NP (RNA binding protein) NS PB2, PA, PB1 (transcription machinery) |
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How many subtypes of HA and NA are there
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HA 16
NA 9 |
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Why are pigs the mixing vessels of influenza?
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Pigs have both human and avian receptors that influenza binds to
human: sialic acid alpha 2,6 galactose avian: sialic acid alpha 2,3 galactose |
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Seasonal flu causes how many infections, severe diseases and mortality per year?
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1 bil infections
3-5 million severe diseases 300-500k mortality |
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The 2009 Swine H1N1 is a reassortment of which strains?
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Human HongKong N3N2 (1968)
Swine H1N2 Eurasian avian-like swine virus Mixed in a pig |
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What makes an influenza strain more pathogenic in terms of its HA?
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Single basic AA: only cleaved by proteases in respiratory/intestinal organs
Multiple basic AA: cleaved by many proteases in many organs, leading to systemic infection. H5 and H7 |
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What are the roles of PA, PB1, PB2?
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PA: cleaves host's 5' cap
PB1: polymerase, uses host's 5' cap as primer PB2: binds host 5' mRNA |
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Name the 2 main targets of Influenza antivirals and the drug names
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Block entry: target M2 ion channel
Amantadine Block exit: target NA (sialidase) Zanamivir, Oseltamivir |
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Which nonstructural protein of influenza modulate the innate immunity of cell? And how does it do that?
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NS2:
limit IFN induction inhibit RIG-I, PKR pathways limit antiviral state inhibit cellular mRNA maturation enhance viral mRNA translation limit apoptosis |
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How can SARS be transmitted?
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Respiratory droplets
Cell-to-cell |
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What is the tropism of SARS?
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lungs, alveolar cells
can be systemic, infect heart and kidney tissues |
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Name the pathogenesis and diseases caused by SARS
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Severe progressive pulmonary disease
Direct epithelial destruction, immune mediated damage Systemic infection Bronchopneumonia (alveolar damage, multinucleation, cytomegaly, nucleomegaly, edema, mononuclear cell infiltration) Kidney cell death |
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Which receptors do SARS bind to?
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ACE-II
L-SIGN (CD209L) |
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Which protein cleaves SARS polyprotein to generate replicase?
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3CLpro
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Where does SARS RNA replication occur?
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cytoplasm
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Which protein contributes to immune evasion of SARS? How?
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Nsp2
1) inhibit translation by binding to 40s (prevents formation of 80s and Nsp2-40s complex removes 5' region of mRNA and IRES) 2) inhibits IFN expression--> inhibits immune response |
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Describe SARS' viral infectivity mechanism
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Host TMPRSS2 (Transmembrane protease serine 2)
cleaves spike to make it less sensitive to neutralizing antibodies |
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Describe the purpose of SARS' manipulation of host protein expression
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Golgi, ER and lysosome are depleted because SARS absolutely require membranes to replicate
Host ribosomes are enriched (to use for replication) |
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What are the two new SARS strains since 2003?
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NL-63 (New Haven)
HKU1 (Hong Kong) |
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What's so special about SARS NL-63?
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4th coronavirus found
Binds ACE-II less efficiently Has unique 179 AA stretch in spike protein Less severe symptoms (flu-like symptoms and no pneumonia) Causes 2ndary bacterial infection (S. pneumoniae) (which increases chance of mortality and pathogenesis) |
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How does SARS NL-63 cause secondary bacterial infection?
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S. pneumoniae's adherence to airway epithelials increase due to the increased expression of PAF-R (platelet activating factor receptor) during NL-63 infection
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What are the current treatments for SARS
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No effective treatments
protease inhibitors (Lopinavir, Ritonavir) IFN treatment Human monoclonal antibodies (to block spike/entry) |
