Area of Expertise: Transcriptional regulation in poxviruses

Poxviruses are a large family of viruses that are pathogenic for many species of mammals, birds, and insects. They are the largest and most complex viruses known, encoding approximately 200 different proteins. The expression of these proteins is developmentally regulated in order to coordinate DNA synthesis and progeny virus packaging. Different classes of genes are turned on or off as the virus progresses through its life cycle. Our laboratory is studying the molecular mechanisms of gene switching.

Poxviruses regulate gene activity primarily at the level of initiation of messenger RNA synthesis. RNA is synthesized by a complex multi-subunit RNA polymerase that is virus-encoded. The choice of gene to be transcribed by the RNA polymerase is dictated by activator proteins specific to each of the three gene classes. Our current interests are in identifying the transcription factors that target the early, intermediate, and late virus genes and subsequently characterizing how they activate transcription. Available evidence indicates that the intermediate and late viral promoters are activated by the same cellular transcription factor. This suggests a model in which the switch from intermediate to late transcription is mediated by a competition between viral intermediate and late factors for interaction with the cellular protein. We are currently testing this hypothesis with the long term goal of understanding how the viral and cellular proteins are integrated into a functional transcription complex.

The adoption of nuclear transcription factors for viral transcription in the cytoplasm implies that the virus can redirect nucleocytoplasmic trafficking of proteins across the nuclear pore complex. Indeed, we have found that nuclear proteins, including transcription factors and soluble enzymes, are redircted to the cytoplasm after virus infection. We are currently investigating how the virus induces thses changes and the properties of the nuclear pore complex that might be altered by the virus.