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Hepatitis A Edit
Hepatitis B Edit
Hepatitis C Edit
was originally identified in 1989, from an agent which was causing transfusion acquired hepatitis (Lindenbach 2007) referred to until HCV as non-A, non-B agent
Hepatitis C effects about 170 million people globally. HCV has a very high replication rate, with en estimated production of 10^12 virions (Lin et al 2007)
Resistance develops quickly due to the high error rate in viral RNA-dependent RNA polymerase, however there are highly conserved regions on the genotype which are drug targets.
genotype 1 HCV 90% of infections?
genotype 1a or 1b
2 and 3 HCV
The structural proteins are in the NH2-terminal region of the polyprotein and the nonstructural proteins (NS) 2 to 5B in the remainder By analogy to related +strand RNA viruses, replication occurs by means of a minus (−) strand RNA intermediate and is catalyzed by the NS proteins forming most likely a cytoplasmic membrane–associated replicase complex.
In 2012, the recommended treatment (Standard of Care) for HCV was a combination pegylated interferon alfa and ribavirin (synthetic nucleoside which induces mutations in viral genes, is a broad spectrum antiviral nucleoside, Patrick 2009)
However this treatment did not induce a sustained response in the main genotype 1 HCV patients. (lin 2006)
ribaviin causes anemia, which are dose limiting. (lin et al calls for novel drugs 2006.)
2 PEG-INF available
2 new drugs boceprevir (BOC) and telaprevir (TLV) which are protease inhibitors where approved in the US.
Other host-related negative predictors of response include older age, male sex, black race, high body mass index (BMI) and presence of co-morbitities.quote FP #4 hep C treatment.
Ghany 2009, Wirth 2010, Hadziyannis 2004, Khattab 2010
SR-BI possibly involved in structural attachment
C protein is targeted to the cytoplasmic surface of the ER
The mechanism of helicase action is incompletely un- derstood and an area of intense interest. NS3 has been shown to unwind RNA and DNA homo- and heterodu- plexes by binding to an unpaired region of a template strand and translocating in a 3 to 5 direction (35). NS3 preferen- tially hydrolyzes adenosine triphosphate (ATP) to power this reaction, but can utilize any standard NTP or deoxynu- cleoside NTP (dNTP). NTPase
# binding. it is thought that HCV use a number of surface receptors, or a receptor complex or corecptors (Lindenbach 2007)
Following attachment, HCV is internalized, presumably via clathrin-mediated endocytosis.
it has been sug gested that interaction of HCV particles with lymphocyte- expressed CD81 may contribute to the disregulated immune response seen in patients with HCV
HCV is associated with HCV-related hepatocellular carcinoma
Hepatitis E Edit