title: Inhibition of host and viral translation during vesicular stomatitis virus infection. eIF2 is responsible for the inhibition of viral but not host translation.
abstract: In cells that allow replication of vesicular stomatitis virus (VSV), there are two phases of translation inhibition: an early block of host translation and a later inhibition of viral translation. We investigated the phosphorylation of the alpha subunit of the eIF2 complex during these two phases of viral infection. In VSV-infected cells, the accumulation of phosphorylated (inactivated) eIF2alpha did not begin until well after host protein synthesis was inhibited, suggesting that it only plays a role in blocking viral translation later after infection. Consistent with this, cells expressing an unphosphorylatable eIF2alpha showed prolonged viral protein synthesis without an effect on host protein synthesis inhibition. Induction of eIF2alpha phosphorylation at early times of viral infection by treatment with thapsigargin showed that virus and host translation are similarly inhibited, demonstrating that viral and host messages are similarly sensitive to eIF2alpha phosphorylation. A recombinant virus that expresses a mutant matrix protein and is defective in the inhibition of host and virus protein synthesis showed an altered phosphorylation of eIF2alpha, demonstrating an involvement of viral protein function in inducing this antiviral response. This analysis of eIF2alpha phosphorylation, coupled with earlier findings that the eIF4F complex is modified earlier during VSV infection, supports a temporal/kinetic model of translation control, where at times soon after infection, changes in the eIF4F complex result in the inhibition of host protein synthesis; at later times, inactivation of the eIF2 complex blocks VSV protein synthesis.
authors.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. jconnor@wfubmc.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Connor
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Lyles
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D051379:Mice; D010766:Phosphorylation; D014176:Protein Biosynthesis; D021122:Protein Subunits / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000235:genetics*; D019284:Thapsigargin / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics* / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D021122:Protein Subunits; D014764:Viral Proteins; D019284:Thapsigargin