Hepatitis Flashcards
HAV basics
enteric transmission - fecal-oral
infectious, self-resolving
ssRNA linear, +
no chronic infection
very low mortality
we make neutralizing IgG which KILLS the virus
can have jaundice etc.
picorna - simar to polio
HBV basics
parenteral
serum hepatitis
dsDNA circulular, para retrovirus
hepadna
HCV basics
parenteral
transfussion
ssRNA linear
chronic in 50% of cases, regardless of age
chronic strongly associated w cirhosis and HCC
HDV
parenteral
increased HBV disease if infect after
ssRNA circular
viroid
HEV basics
enteric: fecal-loral
community acquired
ssRNA linear, + sense
mortality high in immunocompromised
HBV genome
para-retrovirus - does not integrate into chromosomal DNA
replicates by reverse-transcription but packages the DNA intermediate (unlike classic retrovirus)
circular genome - overlapping ORF, barely any room for mutation
acquisition of HBV
newborns of long term carriers
IV drug users
transfusion and ransplant
multiple sex partners
Outcomes of HBV
asymptomatic, acute, fulminant
acute and asymptomatic can become chronic
fulminant hepatitis
viral mutations - replicate so much, directly cytoplastic - 90% mortality
HBV serum particles
particles w no DNA
100x
non infectious - decoys
Stages of HBV infection
- immune tolerance - minimal inflammation and fibrosis (newborns - transplacental tolerance)
- immune clearance - loss of immune tolerance and leads to hepatitis, fibrosis, cirhossis, HCC
- Inactive carrier state - immune control of infection, little hepatitis
- active inflammation - loss of immune control of infection
children primarily have chronic infections from which hepatitis? HBV
HBV - tolerance to virus in utero then infected - don’t fight off as well because tolerance + immune response
can’t clear virus - chronic
Marker for active HBV replication
HBeAg - marker
early antigen is processed and secreted polypeptide of the core protein
secretion of e angiten correlates with viral DNA replication - used as marker for active infection
HBV polymerase protein
RNA and DNA dependent polymerase activity N terminus acts in priming - strand DNA
RNAse H domain - degrade RNA intermediate during replication
HBV life cycle
infect cell (LDL?)
core barticle - inserts genomic material into nucleus
covalently closed (partially gapped/duplexed)
plasmid - cccDNA plasmid
transcribed RNA-DNA intermed, into cytoplasm
translated, package ongoing viral RNA
RNA –> cDNA
bud into ER - vesicluar transport to cell membrane - secrete
Early response to HBV
innate immunity
HBV infected hepatocytes release Type I IFN
Stim HLA class I on hepatocytes
activate NK, NKT –> make IFN, TNF (dictate chronic infection in newbords)
lead to suppression of HBV replication and liver inflammation
Late response to HBV
t cell immunity
CTL priming and recruited, destroy infected hepatocytes
Factors determining acute v chronic HBV infection
age of infected host (newborns more chronic)
strength of cytokine response
immune maturity
treatment of HBV
entecavir or tenofovir (new nt analogs)
adefovir, telbivudine - older nt analogues (less potent, higher resistance
pegylated IFN alpha - once first line, now bottom
VACCINE!!!
HCV transmission
injecting illicit drug use
high risk behaviors in the past
sexual activity
HCV Outcomes
acute infection
subclinical infection (way more common)
chronic liver disease (50%)
HCV life cycle
receptor binding and endoytosis
fusion and uncoating (+ RNA)
translation and protein processing
RNA replication
package it all in cytoplasm
release
NS3
HCV
serine protease
cleave polyprotein and release polypeptide
phosphoprotein
HCV
required for replication
immune editing
HCV
generates large number of variants over infection to evade immune response
pares ag epitopes and evades immune responnse
no neutralizing ab response
generates many variants
why it is so chronic
HCV treatment
RNA dep RNA pol inhibitor - Sovaldi
phosphoprotein replication complex inhibor
Harvoni = combo - approaches 100% long term cure
HCV antiviral
generates many variants
impedes early stages of host response
viral immune editing and glycosylation
disrupts CTLs
serine protease - decreased IFN expression
phosphprotein mutates
HCC Mechanism
apoptic stimulus (viral proteins, CMI) –> cell death –> genetic lesions (mutations, chromosomal instability, continuous proliferation-regeneration) –> resistance to apoptosis –> neoplasia
