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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Chlorocebus aethiops
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Cytoplasmic Granules / genetics
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Cytoplasmic Granules / metabolism*
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Cytoplasmic Granules / pathology
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Cytoplasmic Granules / virology
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DNA Helicases
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DNA Replication / drug effects
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DNA Replication / physiology*
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DNA, Viral / biosynthesis*
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DNA, Viral / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Epoxy Compounds / pharmacology
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Eukaryotic Initiation Factor-2 / genetics
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Eukaryotic Initiation Factor-2 / metabolism
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HeLa Cells
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Herpes Genitalis / genetics
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Herpes Genitalis / metabolism*
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Herpes Genitalis / pathology
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Herpesvirus 2, Human / physiology*
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Humans
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Macrolides / pharmacology
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Phosphorylation / drug effects
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Poly(A)-Binding Proteins / genetics
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Poly(A)-Binding Proteins / metabolism
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Poly-ADP-Ribose Binding Proteins
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RNA Helicases
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RNA Recognition Motif Proteins
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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T-Cell Intracellular Antigen-1
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Thiazoles / pharmacology
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Vero Cells
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Virus Replication / drug effects
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Virus Replication / physiology*
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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DNA, Viral
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DNA-Binding Proteins
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Epoxy Compounds
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Eukaryotic Initiation Factor-2
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KHDRBS1 protein, human
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Macrolides
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Poly(A)-Binding Proteins
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Poly-ADP-Ribose Binding Proteins
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RNA Recognition Motif Proteins
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RNA-Binding Proteins
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T-Cell Intracellular Antigen-1
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TIA1 protein, human
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Thiazoles
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pateamine A
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DNA Helicases
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G3BP1 protein, human
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RNA Helicases