Hepatitis B virus (HBV) is the most prevalent human tumor virus and causes most virus-associated human cancers. It is estimated that chronic HBV infection cause 500,000 causes of live cancer annually. HBV must actively replicate within liver cells to maintain its chronic infection. Dr. Loeb and colleagues work to understand how HBV carries out the individual steps by which it replicates its genome in order to understand how this virus contributes to human cancer. HBV replicates its genome by a reverse transcription pathway, which involves switching templates three times during the course of DNA synthesis. Dr. Loeb and colleagues will pursue several complementary goals to understand the mechanisms of each of the three templates switches that are required for genome replication of HBV. First, they will define the cis-acting elements of the nucleic acid template required for each of the three template switches. Concomitant with these analyses, they will characterize the ability of viruses with mutations within these cis-actin sequences to carry out the relevant template switch, with the goal of gaining insights into mechanisms underlying these switches. Lastly, they will identify other viral components, either nucleic acid or protein, that are specifically involved with each of the template switches, using complementary approaches.
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