pateamine-a and Herpes-Genitalis

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.

Topics: Adaptor Proteins, Signal Transducing; Animals; Carrier Proteins; Chlorocebus aethiops; Cytoplasmic Granules; DNA Helicases; DNA Replication; DNA-Binding Proteins; DNA, Viral; Epoxy Compounds; Eukaryotic Initiation Factor-2; HeLa Cells; Herpes Genitalis; Herpesvirus 2, Human; Humans; Macrolides; Phosphorylation; Poly-ADP-Ribose Binding Proteins; Poly(A)-Binding Proteins; RNA Helicases; RNA Recognition Motif Proteins; RNA-Binding Proteins; T-Cell Intracellular Antigen-1; Thiazoles; Vero Cells; Virus Replication