Zeng- Hep- Melissa Flashcards
Where is HAV incidence high?
- Highest in developing Asian and african countries
- Incidence substantially decreased in US with introduction of vaccine
Describe HAV:
Family, genome, structure
Picornaviridae
(+) ssRNA
Naked, icosahedral capsid (VP1-3), spherical structure
Describe the neutralizing antigenic epitope for HAV
What does our immune system recognize?
- CONFORMATIONAL EPITOPE vs. typical 3 aa sequence
- VP1 + VP3 form specific structure recognized by human immune system
What is significant about the 5’ noncoding region of HAV genomic RNA?
- IRES (internal ribosomal entry sequence) on 5’ cap
- Forms secondary structure required for cap independent translation (no 5’ cap)
Describe the translational products of HAV mRNA
- RNA has single open reading frame (ORF)
- Yields single translational (protein) product
- Product is cleaved into structural and regulatory proteins
What are risk factors for HAV infection? (3)
- poor sanitation/ travel to endemic locations
- MSM
- IV drug use
What is the primary route of transmission for HAV in endemic areas? In the US?
Endemic areas: fecal-oral
USA: IV drug use/ MSM
Describe two means by which HAV is particularly virulent as an enteric virus
- heat stable (cook to 121F/60C for 30 min)
- acid and detergent stable
How does HAV mediate damage to the liver?
Which immune cells are dominant during acute infection and recovery?
Immune mediated damage to hepatocytes
- CTLs predominate in acute phase of infection
- NK mediated lysis of HAV infected hepatocytes
- CD4+ T cells dominate in recovery phase
Do patient develop long lived immunity against HAV after infection? Is vaccination possible?
- Yes, long lived Abs against VP1, VP3 conformational epitope confirm protective immunity
- Thus, vaccination is very effective
Where geographically is HBV incidence highest?
Most common in Asia; 2 billion infections ww/ year
HBV:
Family, genome, structure
What are the important antigens associated with the structure?
HepaDNAviridae family
- Relaxed, partially circular dsDNA
- Capsid (HBcAg)
- Enveloped (HBsAg x3, long, medium, short)
**Note: pre-core HBeAg is secreted during replications and indicates INFECTIVITY
Describe the 3 types of HBV viral particles:
- Dane particle = spherical; complete infectious viron, contains genome
- Filamentous subviron= noninfectious, no genome
- Spherical subviron= noninfectious, no genome
Describe 4 important characteristics of HBV genome:
What is meant by relaxed circular DNA?
What are two important features of the 5’ end?
What is one feature that facilitates economic usage of the genomic material?
- Relaxed circular (noncovalently closed) partially dsDNA
(inner (+) strand not full length) - Polymerase ATTACHED @ 5’ end
- RNA primer (PROTEIN) attached at 5’ end
- Overlapping reading frames (mult. reading frames)
Describe the HBV viral life cycle:
Attachment–> nuclear capsid released–>
Nuclear capsid transported to nuclear cell membrane–>
RC DNA released into nucleus–>
Removal of polymerase + RNA from RC DNA–>
DNA synth + ligation ( “repair”) –>
**cccDNA synthesis complete–>
Viral minimicrosome–> Transcription of VIRAL RNA–>
VIRAL RNA exported to cytoplasm –>
Subgeneric + Genomic HBeAg Transcripts–>
Genomic replication–> Assembly of viral particle–> Release
**cccDNA = covalently closed circular DNA
What is HBxAg?
Subgeneric transcript formed furring translation of HBV RNA: this confers ability to transform into hepatocellular carcinoma
What are the two important genomic length transcripts synthesized turing translation of HBV RNA transcripts?
What are their functional purposes?
- Precore RNA: codes for HBeAg (secreted, indicates infectivity)
- Pregenomic RNA (pgRNA): shorter than precore; no start codon for HBeAg
- encodes viral polymerase + HBcAg
- template for genomic DNA synthesis
Describe the details of genomic replication:
Epsilon structure on 5' pgRNA binds HBV pol + HBcAg--> Immature nucleocapsid--> HBV polymerase activity (TP primes, RT reverse transcribes)--> Pol-DNA oligo complex forms--> Pairs with 3' pgRNA--> Reverse transcription of pgRNA--> (-) strand DNA synthesized--> Serves as template for (+) strand
List the 3 specific functions od 5’ Epsilon stem loop structure on pgRNA:
- pol binding site
- template for DNA oligo synthesis
- encapsidation signal (associates with HBcAg)
What are the three domains of HBV polymerase and what are their functions:
TP (Terminal protein) = PROTEIN PRIMER for RT initiation
RT = reverse transcriptase
RH = RNase H
Describe the final formation of a complete HBV viral particle:
HBsAgs cluster on ER membrane–>
LHBsAg + HBsAg interact–>
Pull nucleocapsid into HBsAg cluster–>
Budding into ER lumen–> secretion
What are HBV quasisecies?
HBV polymerase lacks proofreading capacity; genome highly prone to mutation
Mixture of genetic variants = quasi species
How is HBV transmitted in endemic vs. non endemic areas?
At what age will infection lead to higher rate of chronicity?
Endemic:
PERINATAL INFECTION; can be monitored by HBeAg titers; BREASTFEEDING NOT RISK FOR TRANSMISSION
**INFECTION AT YOUNG AGE = ^^ CHRONICITY
Non-endemic:
Sexual + percutaneous spread; low rate of chronicity because patients infected later in life
How is hepatic injury mediated in HBV infection?
Describe the humoral response, noncytolytic clearance, and the inlammatory response to infection.
Is there long term immunity after infection subsides?
Mediated by IMMUNE RESPONSE
Humoral Anti-HBsAg are protective (long term immunity)
Noncytolytic clearance: CTLs–> IFNY, TNFa, IFNa/b
- Occurs AFTER peak replication, BEFORE hepatitis onset
Inflammatory Response: Acute HBV (Specific CD4, CD8)--> Nonspecific T, NK, Neutros
HCV
Viral classification, prevalence, mode of transmission?
Flavaviridae, (+)ssRNA
2% ww, most common in Egypt
Transmitted via IV drug use
HCV: Describe the mechanism of infection
HCV E1, E2 heterodimer interacts with cell surface CD81, SR-B1–> weak, delayed cellular and humoral immune response–> mild clinical sx w ^^ chronicity
HDV:
Viral classification, prevalence, mode of transmission?
Deltaviridae, covalent circular (-) RNA
Up to 30% HBV + patients in cold areas have this
Transmitted parenterally (IV drugs use)
HDV: Describe the mechanism of infection
Satellite virus (defective) needs HBV coinfection/ superinfection carriers in order to infect
HEV:
Viral classification, prevalence, mode of transmission?
Calcaviridae, (+) ssRNA
#1 form of hepatitis in endemic regions (70% ppl get it)
Fecal oral transmission especially during WET SEASONS
HEV: Describe mechanism of infection
Unidentified cell receptor
