| Chemical and genetic inhibitors of polyomavirus infection |
The laboratory is interested in identifying cellular genes and proteins required for successful virus infection and in characterizing their role in infection. By using genome-wide RNA interference screens and high-throughput chemical screens we have identified several genes that are required for infection by SV40 and related human polyomaviruses, as well as small molecules that inhibit infection by these viruses. The genes required for infection encode cell surface molecules that appear involved in the initial steps of virus-cell interaction, as well as intracellular proteins that appear to play a role in capsid disassembly and delivery of the viral DNA to the nucleus. The inhibitory chemicals also block in the early phase of infection, and may represent candidate lead compounds for new anti-viral drugs effective against diseases caused by the pathogenic human polyomaviruses, such as polyomavirus-induced nephropathy. In addition, we have initiated a siRNA screen to identify cellular genes required for infection by the high-risk human papillomaviruses (HPV). Reference: Goodwin, E.C., Atwood, W.J., and DiMaio, D. (2009) High-throughput, cell-based screen for chemicals that inhibit infection by SV40 and human polyomaviruses. J. Virol.83:5630-5639. doi:10.1128/JVI.00203-09. |