Poxviruses: Translation & Innate Immunity

Members of the poxvirus family include Variola Virus (VarV), the causative agent of smallpox, and Vaccinia Virus (VacV), a close relative that was used as a vaccine against smallpox and which has become the laboratory prototype for poxvirus research. These large double-stranded DNA viruses exhibit an impressive level of self-sufficiency and encode many of the proteins required for transcription and replication of their DNA genomes. Indeed, unlike many other DNA viruses, poxviruses do not require access to the host nucleus and replicate exclusively in the cytoplasm of infected cells within compartments termed Viral Factories. Because of this unusual mode of replication, this leaves poxviruses vulnerable to detection by cytosolic sensors such as cGAS. Moreover, despite their self-sufficiency, like all viruses, they remain dependent on gaining access to host ribosomes in order to translate their mRNAs into proteins.

Our work focuses on how to main areas of poxvirus biology:

1) Understanding how VacV gains control of the host translation system to replicate, with a particular focus on how these viruses directly target and control host ribosomes, as well as upstream regulatory signaling pathways.

2) Understanding how VacV targets mTOR signaling to control innate immune responses, which we have recently found are orchestrated by mitochondria at later stages of virus replication.