Northwestern University Feinberg School of Medicine

Derek Walsh Lab

Poxvirus & 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 the function of two eukaryotic translation initiation factor (eIF) complexes, eIF3 and eIF4F, that regulate ribosome recruitment to capped mRNAs and their role in VacV infection. We have found that VacV stimulates the assembly of eIF4F complexes and that this is important for both viral protein synthesis and control of host immune responses. Furthermore, we have found that eIF3 functionally communicates with eIF4F during translation initiation, and that this plays an important role in VacV replication. Finally, we have also found that VacV redistributes key eIF4F subunits to specific regions within viral factories, a process that appears to involve the viral I3 protein. Projects in our lab are currently focused on exploring the role of translation during VacV infection and host antiviral responses, with particular emphasis on cell signaling pathways and eIF4F.

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

Small pox virus
Smallpox virus: Courtesy of the CDC Public Health Image Library