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Hepatitis C And Cellular Biology Hepatitis C

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Hepatitis C and Cellular Biology Hepatitis C is a virus that affects over 2% of the global population (Belon & Frick, 2009). It is a virus that leads to chronic liver disease, and has many complications, including cirrhosis, fibrosis, and hepatocellular carcinoma (Belon & Frick, 2009), and it is the leading cause of liver transplantation among...

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Hepatitis C and Cellular Biology Hepatitis C is a virus that affects over 2% of the global population (Belon & Frick, 2009). It is a virus that leads to chronic liver disease, and has many complications, including cirrhosis, fibrosis, and hepatocellular carcinoma (Belon & Frick, 2009), and it is the leading cause of liver transplantation among countries in the developed world (Whidby et al., 2009). Hepatitis C establishes and maintains a life-long infection in individuals despite the fact that the virus is detected and targeted by immune mechanisms of the host (Sharma, 2010).

The virus survives and persists due to rapid mutations that allow the virus to escape surveillance by immune mechanisms (Sharma, 2010). The hepatitis C virus itself is a very small hepatotropic RNA virus that is enveloped and spherical (Sharma, 2010). The only available treatment option for Hepatitis C is administration of a long-acting pegylated-interferon-alpha in combination with nucleoside analog ribavirin (Sharma, 2010). This treatment has been demonstrated as only moderately successful at best (Sharma, 2010). Currently there are no selective antiviral therapies or vaccines for prevention available (Sharma, 2010).

The discovery of new therapies for the treatment of Hepatitis C is complicated by the complex lifecycle of the virus (Sharma, 2010). The efficacy of treatment depends mostly on the initial viral load and the infecting strain of the virus (Whidby et al., 2009). A major obstacle for the development of viable therapies for hepatitis C was the failure scientists experienced in trying to replicate and produce the virus in cell culture (Sharma, 2010).

In 2005, however, an in vitro cell culture system was developed for hepatitis C This development allowed researchers to effectively investigate the complete lifecycle of the virus (Sharma, 2010). This opened a doorway into the potential development of effective antiviral therapies and preventative vaccines. At present, there are no approved antiviral therapies specifically targeted at hepatitis C The advances in understanding of the lifecycle of the virus have enabled the development of various inhibitors and anti-viral agents, which are currently in clinical trials (Sharma, 2010).

The inhibitors under development and clinical investigation target several hepatitis C receptors, including NS3/4A, HCV-IRES, NS5A, and NS5B (Sharma, 2010). Also, the inhibition of alpha-glucosidase enzyme by inhibitors like celgosivir, n-butyl deoxynojirimycin and N-(n-nonyl) deoxynojirimycin offers therapeutic option since they affect morphogenesis of the virus (Sharma, 2010). A study by Whidby et al. (2009) demonstrated how infection by the hepatitis C virus may be blocked by a form of envelope protein 2 ectodomain.

These researchers recognized that infection by the virus occurs by endosomal acidification, which indicates the involvement of pH in the fusion of the viral envelope with cellular membranes (Whidby et al., 2009). Therefore, the researchers developed a production system for a secreted form of E2 ectodomain from mammalian cells (Whidby et al., 2009). This was demonstrated to be effective in blocking infection by cell culture-derived hepatitis C virus, which may lead to further advances in the development of vaccines and entry inhibitors for the virus (Whidby et al., 2009).

Belon & Frick (2009) suggest that antiviral therapies specifically targeted for hepatitis C will prove to be the most effective treatments, replacing presently used therapies. These include all new antiviral agents that act upon the proteins that are involved in the replication of the virus (Belon & Frick, 2009). These researchers looked specifically at compounds that seem to inhibit catalyzed reactions of the hepatitis C virus helicase and cellular replication of the virus (Belon & Frick, 2009).

Some of the findings involving hepatitis C helicase inhibitors discussed included nucleoside and base analogs called benzatriazoles that inhibit the virus in virto, and a new beacon-based molecular helicase assay that has been developed for the facilitation of the analysis of inhibitors (Belon & Frick, 2009). Advances have also been made with regard to the development of vaccines for the prevention of hepatitis C Clinical trials are currently underway to test the effectiveness of IC41, which is a synthetic peptide vaccine that contains hepatitis C virus T-cell epitopes (Sharma, 2010).

IC41 has been shown to induce INF-gamma-secreting CD$+ and CD8+ T-cells specific to the hepatitis C virus in healthy individuals, and it has been demonstrated to induce Th 1/Tc 1 responses that are specific to the virus.

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