Molecular Basis of Cytokine-Induced Clearance of HBV DNA

Scripps Research Institute, La Jolla CA

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Abstract

DESCRIPTION: (Adapted from the Investigator's abstract): Hepatitis B Virus (HBV) can establish either a chronic or acute infection in infected individuals. Although cytotoxic T-lymphocyte (CTL)-mediated killing of infected hepatocytes likely plays an important role in the outcome of infection, HBV replication and gene expression are also strongly inhibited by non-cytolytic mechanisms mediated by the cytokines interferon alpha/beta, interferon gamma, and tumor necrosis factor alpha. The cytokine-mediated inhibition of HBV replication is likely to be critically important for clearance of the virus while protecting the liver from extensive CTLmediated damage. Although it has been demonstrated that the cytokine-mediated inhibition of HBV replication occurs at the level of assembly or stability of viral pre-genomic RNA-containing capsids, the mechanism by which this process occurs and the cellular proteins involved have not been determined. The focus of this proposal is to identify cellular proteins that interact with HBV core antigen in a cytokine-regulated manner, and to determine the relevance of these interactions to the clearance of HBV replicative intermediates from infected cells.