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.