title: Herpes simplex virus 2 infection impacts stress granule accumulation.
abstract: Interference with stress granule (SG) accumulation is gaining increased appreciation as a common strategy used by diverse viruses to facilitate their replication and to cope with translational arrest. Here, we examined the impact of infection by herpes simplex virus 2 (HSV-2) on SG accumulation by monitoring the localization of the SG components T cell internal antigen 1 (TIA-1), Ras-GTPase-activating SH3-domain-binding protein (G3BP), and poly(A)-binding protein (PABP). Our results indicate that SGs do not accumulate in HSV-2-infected cells and that HSV-2 can interfere with arsenite-induced SG accumulation early after infection. Surprisingly, SG accumulation was inhibited despite increased phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), implying that HSV-2 encodes previously unrecognized activities designed to maintain translation initiation downstream of eIF2α. SG accumulation was not inhibited in HSV-2-infected cells treated with pateamine A, an inducer that works independently of eIF2α phosphorylation. The SGs that accumulated following pateamine A treatment of infected cells contained G3BP and PABP but were largely devoid of TIA-1. We also identified novel nuclear structures containing TIA-1 that form late in infection. These structures contain the RNA binding protein 68-kDa Src-associated in mitosis (Sam68) and were noticeably absent in infected cells treated with inhibitors of viral DNA replication, suggesting that they arise as a result of late events in the virus replicative cycle.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Renée L
authors.initials: RL
authors.lastname: Finnen
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Pangka
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Banfield
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004265:DNA Helicases; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology*; D004279:DNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006558:Herpes Genitalis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D039102:Poly(A)-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1; D013844:Thiazoles / Q000494:pharmacology; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D004852:Epoxy Compounds; D015852:Eukaryotic Initiation Factor-2; C489559:KHDRBS1 protein, human; D018942:Macrolides; D039102:Poly(A)-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D013844:Thiazoles; C421324:pateamine A; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases