Hepatitis C Flashcards
Viral hepatitis
- inflammation of liver
- wide spectrum asymptomatic–>acute –> fuminant
- non-specific symptoms
Identification of hepatitis C virus
- NANBH known to cause chronic infections
- cirrhosis and chronic liver disease
- acute hepatitis =asymptomatic
- HCV accounts for around 30% liver transplants
HCV cloning
- eventually cloned in 1989
- initial difficulty due to inability to grow in culture
HCV virion morphology
- difficult to detect (low levels of virus in plasma)
- 50nm spherical particles
- enveloped
- react with antibodies to HCV
HCV Classification and genome structure
- flavivirus family
- new genus called HEPACIVIRUS
- enveloped RNA genome
- positive sense (same as mRNA)
- 10Kb genome encodes structural (s) and non structural (NS) proteins flanked by regulatory elements
- S-env, core and p7
- NS - viral enzymes and cofactors
- processed/cleaved by viral and cellular proteases
HCV Replication Cycle
- Receptor binding (CD81,SRB1, Claudin & Occludin)
- Endocytosis
- Membrane fusion (low pH dependent)
- Uncoating
- Translation/processing
- RNA replication
- Virion morphogenesis
- Virion transport and glycoprotein maturation
- Fusion and virion release
HCV Protein fuctions:
S (structural)
-env - receptor binding
-p7 -ion channel
-Core - maintenance of the genome
NS (nonstructural)
-enzymes and cofactors
-HCV core protein binds to the p53 promoter (blocking expression of p53)
-allows proliferation of cells with DNA damage
-can lead to hepatocellular carcinoma (HCC)
Results of HCV infection
-a chronic infection
-Ab and cytotoxic T-cell production -liver inflammation
-Liver cirrhosis
-Hepatocellular carcinoma (HCC)
80% of HCCs are viral (60%HBV) and (40% HCV)
Factors promoting severity
- alcohol
- age
- co-infection HIV
- male gender
- chronic HBV co-infection
New vaccine
-strong and broad immune responses
What % of poeple with chronic infection are unaware?
80%
-small % will develop HCC
