Grant: Operating Grant - PA: Institute of Genetics (Bridge Funding)

We use viruses to study how nuclear structures regulate gene expression. These studies may also lead to novel antivirals. We and many others have preliminary evidence that cells attempt to inactivate infecting virions by a process called silencing, which involves so called epigenetic regulation. This process is also used to regulate cellular gene expression during development and disease (such as cancer). In this application, we propose to further characterize this cellular response to infection. As viruses are most tractable systems, we expect that our experiments will further advance our understanding of the epigenetic mechanisms that regulate cell differentiation. Our research may also allow us to design in the near future novel antiviral drugs to activate these cellular defenses. Antiviral drugs are commonly designed to target viral protein, which assures that the targets of the drug are present only in infected cells, thus minimizing toxicity toward other cells, but leading to drugs that select for resistant viral strains. Antiviral drugs that target cellular proteins, in contrast, do not select for viral resistance as promptly because mutations on the viral genome (the cause of resistance) have no impact on the targets of such drugs.