Northwestern University Feinberg School of Medicine

Derek Walsh Lab

Poxviruses & Translation

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”. However, like all viruses, they remain dependent on gaining access to host ribosomes in order to translate their mRNAs into proteins and must also counteract host antiviral responses aimed at crippling the translation system to prevent virus replication.

Our work focuses on how VacV gains control of the host translation system to replicate. This includes studies of eukaryotic initiation factors and ribosomes, as well as upstream regulatory signaling pathways as both targets for viral manipulation and in host responses to infection.

Host translational factors
Host translation factors (yellow) localized to poxvirus factories in the cytoplasm of infected cells. Host cell nuclei are blue.

VacV modifies RACK1 (blue) on the 40S ribosome to enhance viral mRNA translation.
VacV modifies RACK1 (blue) on the 40S ribosome to enhance viral mRNA translation.