Sequestration of G3BP coupled with efficient translation inhibits stress granules in Semliki Forest virus infection.

Abstract	Dynamic, mRNA-containing stress granules (SGs) form in the cytoplasm of cells under environmental stresses, including viral infection. Many viruses appear to employ mechanisms to disrupt the formation of SGs on their mRNAs, suggesting that they represent a cellular defense against infection. Here, we report that early in Semliki Forest virus infection, the C-terminal domain of the viral nonstructural protein 3 (nsP3) forms a complex with Ras-GAP SH3-domain-binding protein (G3BP) and sequesters it into viral RNA replication complexes in a manner that inhibits the formation of SGs on viral mRNAs. A viral mutant carrying a C-terminal truncation of nsP3 induces more persistent SGs and is attenuated for propagation in cell culture. Of importance, we also show that the efficient translation of viral mRNAs containing a translation enhancer sequence also contributes to the disassembly of SGs in infected cells. Furthermore, we show that the nsP3/G3BP interaction also blocks SGs induced by other stresses than virus infection. This is one of few described viral mechanisms for SG disruption and underlines the role of SGs in antiviral defense.
Authors	Marc D Panas, Margus Varjak, Aleksei Lulla, Kai Er Eng, Andres Merits, Gunilla B Karlsson Hedestam, Gerald M McInerney
Journal	Molecular biology of the cell (Mol Biol Cell) Vol. 23 Issue 24 Pg. 4701-12 (Dec 2012) ISSN: 1939-4586 [Electronic] United States
PMID	23087212 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing Carrier Proteins G3BP2 protein, human Nsp3 protein, semliki forest virus Poly-ADP-Ribose Binding Proteins RNA Recognition Motif Proteins RNA, Messenger RNA-Binding Proteins Viral Nonstructural Proteins Green Fluorescent Proteins DNA Helicases G3BP1 protein, human RNA Helicases
Topics	Adaptor Proteins, Signal Transducing Animals Binding Sites (genetics) Carrier Proteins (genetics, metabolism) Cell Line Cells, Cultured Cytoplasmic Granules (metabolism, virology) DNA Helicases Green Fluorescent Proteins (genetics, metabolism) HEK293 Cells Host-Pathogen Interactions Humans Immunoblotting Mice Microscopy, Confocal Mutation Poly-ADP-Ribose Binding Proteins Protein Binding Protein Biosynthesis RNA Helicases RNA Recognition Motif Proteins RNA, Messenger (genetics, metabolism) RNA-Binding Proteins (genetics, metabolism) Semliki forest virus (genetics, metabolism, physiology) Stress, Physiological Viral Nonstructural Proteins (genetics, metabolism)

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