hepatitis Flashcards
Hepatitis
a clinical syndrome characterized by
inflammation of the liver
why is jaundice associated with hepatitis
hepatocyte cell death releases bilirubin, which causes jaundice
bilirubin is a biproduct of heme metabolism in the liver (where heme is detoxified)
hepatitis viruses trophism
strong tropism for the liver and preferentially replicate in the hepatocyte
85% of liver cells are hepatocytes
Therefore these viruses primarily cause liverdisease
2 main modes of action for hepatitis viruses
strains?
transmission
HepA genome and family
linear +ssRNA
picornaviridae
HepA causes what kind of hepatits
infectious hepatitis
HepA strucutre
icoshedral naked capsid
HepA transmission
spread by fecal-oral contamination of food, drink, or shellfish
HAV shedding/ effect on hepatocytes
HAV shed into bile ducts and into intestine and passes out of the body in the feces
HAV directly kills hepatocytes
clinical manifestation of HAV infection (HepA)
–usually mild intestinal infection
–occasionally viremia occurs, leading to liver infection= jaundice
prevention and treatment HAV
killed HAV vaccine (now recommended for all in US, esp. for military, frequent travelers, staff of care facilities)
Post-exposure immune globulin
HAV highly endemic regions: children and adult from non endemic regions
In highly endemic regions, almost all children become infected in first few years of life
- most remain asymptomatic
- adults from nonendemic regions who become infected are more likely to display
symptoms
HepB genome and family
nicked circular, mostly dsDNA
hepadnaviridae
Hep B envelope
enveloped
genome size HepB
smallest at 3200 bp
viral particles of hepB
–22 nm particle
–Variable tubular/filamentous particle (22 nm diameter)
–42 nm Dane particle (infective form of virus)
surface Ag of HepB
L,M, and S, embedded in the lipid bilayer envelope
HBsAg-S is the main component
core Ag of hepB, useful?
HBeAg is a processed form of the core, HBcAg.
HBeAg is mostly secreted from infected cells and found in bloodstream. Useful marker for HBV infection.
filament form of hepB enriched for?
HBsAg-L
HepB replication cycle
receptor mediated endo
core particle enters host nuc
undergoes repair to form full dsDNA circle
use of host RNA transcriptase
RNA out of nuc may be translated
RT occurs during viral assembly, unlike retroviruses (DNA made), Reverse transcription is by
viral reverse transcriptase
Budding from ER and vesicular transport to cell mem for release
HepB RT priming
Priming of reverse transcription by TP (terminal protein domain) of viral polymerase by adding first nucleotide to a tyrosine residue of TP
what determine course of HepB infection
Cell-mediated immune response- Cytotoxic T lymphocytes kill infected hepatocytes
effective CMI with HepB
non-effective CMI with HepB
how does HBV kill hepatocytes
HBV does not directly kill hepatocytes
Cytotoxic T lymphocytes directed against MHC class I proteins bound to viral antigens on hepatocyte surface
Killing also occurs by cytokine release that promotes inflammation and tissue damage
Outcomes of acute HBV infection
infants and HBv infection outcome
90% become chronically infected due to not fully developed Immune response
Hepatocellular carcinoma - why?
increased cell division due to regeneration - increases chances of mutations
peroxides and free radicals from CTL killing
Serology of HBV infections HbsAg, ANTI Hb s, ANTI Hb c, ANTI Hb e, HbeAg no exposure prior vax resolved acute infection acute/chronic infection late stage chronic
prevention HepB
HBsAg particles produced in?
vaccination recommended for all infants in USA
–HBsAg particles produced in yeast
treatment HepB
–passive immunotherapy within 7 days of exposure
anti RT drugs
HepD genome and family
circular -ssRNA
deltaviridae
HDV depends on what other Hep and why
Depends on HBV virus to replicate (provides
envelope protein)
chronic HBV and HDV
Chronic HBV infection exacerbated by infection with hepatitis delta virus
HepC genome and family
linear +ssRNA
flaviviridae
HepC envelope?
enveloped
HCV spread routes
In addition to HCV transmission through blood and sexual
fluid, HCV also spreads from mother to fetus, by fecal-oral
route, and through organ transplants
how does HCV kill hepatocytes
HCV also does not directly kill hepatocytes
Cytotoxic T lymphocytes directed against MHC class I proteins bound to viral antigens on
hepatocyte surface
Killing also occurs by cytokine release that promotes inflammation and tissue damage
HCV replication cycle
receptor binding and endo uncoating \+RNA translated/ polyprotein made = RNA poly made RNA replication (+ to - then to more +) virion assembly and release
HCV RNA poly error
Viral RNA polymerase is error-prone, creating multiple viral variants (= quasi-species) (like HIV)
HCV infection outcomes
HepE genome and family
linear + ssRNA
caliciviridae
HepE replication cycle
receptor endo
uncoating and translation of RNA = polypro = viral RNA poly
replication of RNA = full genome and subgenomic for more proteins
assembly and release without budding (naked capsid virus)
HepE transmission
spread in contaminated food and drink (like HAV)
• human-to human transmission and animal-to-human transmission (common source = pigs) (zoonosis).
HEV shedding/ effect on hepatocytes
HEV shed into bile ducts and into intestine and passes out of the body in the feces
HEV directly kills hepatocytes
