Hepatitis C virus (HCV) is a major health problem with as many as 3.9 million Americans chronically infected. As the population ages, these patients will be at increasing risk of developing liver disease and hepatocellular carcinoma. The current model for HCV study, the chimpanzee, is too large and too expensive for extensive use as a model for HCV infection. An alternative surrogate model for HCV infection might be replication of the hepatitis GB virus B (GBV-B) agent 'in tamarins. The GBV-B virus is flavivirus-like and is related to HCV. GBV-B has a similar genomic structure and its protease shares substrate specificity with the HCV protease. GBV-B is believed to be a tamarin virus that causes an acute, self-limiting hepatitis. The virus can be transmitted via infectious plasma causing a readily reproducible hepatitis. This proposal is to develop GBV-B infection of tamarins as a model for HCV infection. Tamarins will be infected with GBV-B to generate reagents necessary for further study of this virus. Hepatocytes from infected and uninfected animals will be isolated to study GBV-B infection in the absence of an immune response and to determine whether primary hepatocytes or hepatocyte cell lines will be permissive for GBV-B infection. The cell-mediated immune response to GBV-B infection in tamarins will be investigated to determine how it differs from the human immune response to HCV infection. Tamarins will be immunosuppressed to determine whether a chronic infection by GBV-B can be induced that will more closely resemble an HCV infection. Owl monkeys and spider monkeys will also be tested for their susceptibility to GBV-B infection. It is hoped that a viable surrogate model for HCV infection will be developed.
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