Many viruses establish chronic infections that persist for the lifetime of their hosts. Some of these viruses, including the human immunodeficiency virus and the hepatitis B (HBV) and C viruses, are associated with a large degree of worldwide morbidity and mortality. Current therapies for these diseases are only moderately effective, and are often limited by a number of variables including cost, significant side effects, and viral resistance to the drugs. Therefore, new and improved therapies for these diseases are needed. Our laboratory studies the host-pathogen interactions related to HBV infection. Approximately 350 million people worldwide are chronically infected with HBV, including an estimated 1.25 million in the United States. HBV infection leads to millions of deaths each year from liver diseases such as cirrhosis and hepatocellular carcinoma. We are exploring three unique therapeutic approaches to treat this disease. First, we are investigating the relationships between HBV and cellular regulatory pathways, as these may be exploited pharmacologically to block virus replication. Second, we are characterizing the ability of novel antiviral and immunomodulatory cytokines to inhibit HBV replication and prevent liver damage. Third, we are studying new methodologies for therapeutic vaccination to boost the immune response to HBV in people who are chronically infected. These studies have the potential to expand the repertoire of antiviral therapies beyond those currently being employed, and therefore significantly impact public health.
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