title: Recruitment of host translation initiation factor eIF4G by the Vaccinia Virus ssDNA-binding protein I3.
abstract: Poxviruses are large double-stranded DNA viruses that replicate exclusively in the cytoplasm of infected cells within discrete compartments termed viral factories. Recent work has shown that the prototypical poxvirus, Vaccinia Virus (VacV) sequesters components of the eukaryotic translation initiation complex eIF4F within viral factories while also stimulating formation of eIF4F complexes. However, the forces that govern these events remain unknown. Here, we show that maximal eIF4F formation requires viral DNA replication and the formation of viral factories, suggesting that sequestration functions to promote eIF4F assembly, and identify the ssDNA-binding protein, I3 as a viral factor that interacts and co-localizes with the eIF4F scaffold protein, eIF4G. Although it did not adversely affect host or viral protein synthesis, I3 specifically mediated the binding of eIF4G to ssDNA. Combined, our findings offer an explanation for the specific pattern and temporal process of eIF4G redistribution and eIF4F complex assembly within VacV-infected cells.
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Zaborowska
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kellner
authors.forename: Michael
authors.initials: M
authors.lastname: Henry
authors.forename: Paula
authors.initials: P
authors.lastname: Meleady
authors.forename: Derek
authors.initials: D
authors.lastname: Walsh
mesh_terms: D002460:Cell Line; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D039562:Eukaryotic Initiation Factor-4F / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D006801:Humans; D010442:Peptide Chain Initiation, Translational; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C113920:EIF4G1 protein, human; D039562:Eukaryotic Initiation Factor-4F; D039603:Eukaryotic Initiation Factor-4G; C111416:I3 protein, Vaccinia virus; D014764:Viral Proteins