Molecular Mechanisms of Hepatitis C Virus entry.

Funded Activity Summary

Hepatitis C virus (HCV), the main cause of of post-transfusion and community -acquired non-A, non-B hepatitis, infects approximately 170 million humans world-wide with some 135,000 infections in Australia alone. HCV is hyper-endemic in intravenous blood users with typical prevalence rates of 60-70%. About 75-80% of infected individuals develop a chronic infection, usually resulting in recurrent, progressively worsening liver damage. Cirrhosis develops in 10-20% of chronic cases while 1-5% of chronic carriers develop liver cancer. Development of an effective vaccine is complicated due to the highly variable nature of the virus. Approved therapies include alpha-interferon and alpha interferon-ribavirin combinations but these treatments induce efficacious responses in only 20-30% of patients and often have severe side-effects. It is assumed that after attachment of HCV to the cell surface, the virus is internalised by the cell and undergoes fusion with a cellular compartment referred to as an endosome. The low pH environment of the endosome is presumed to trigger viral fusion via its cell surface glycoproteins and empties the replication machinery of the virus into the cell. No reliable systems for the propagation of HCV are available thereby limiting studies into the mechanisms of how HCV infects cells and the development of vaccines. Recently a cell surface molecule, CD81, was identified as a possible receptor for the attachment of HCV to susceptible cells. Our aim is to 1) develop model systems for studying HCV entry and fusion and 2) further characterise the interaction of the HCV glycoproteins with CD81 with the goal of obtaining a three-dimersional structure of the interaction . These studies will address the fundamental questions of how HCV enters cells leading new avenues for the design of inhibitors of HCV entry.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $362,545.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Applied immunology (incl. antibody engineering xenotransplantation and t-cell therapies)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Chronic disease caused by hepatitis C virus infection | Hepatitis C virus | Hepatitis C virus infection | Hepatocelullar carcinoma | Membrane fusion | Viral glycoproteins

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