Inhibition of cytoplasmic mRNA stress granule formation by a viral proteinase.
Mammalian cells form dynamic cytoplasmic mRNA stress granules (SGs) in response to environmental stresses including viral infections. SGs are involved in regulating host mRNA function and metabolism, although their precise role during viral infection is unknown. SGs are thought to assemble based on functions of the RNA-binding proteins TIA-1/TIAR or Ras-GAP SH3 domain-binding protein (G3BP). Here, we investigated the relationship between a prototypical plus-strand RNA virus and SGs. Early during poliovirus infection, SG formation is induced, but as infection proceeds this ability is lost, and SGs disperse. Infection resulted in cleavage of G3BP, but not TIA-1 or TIAR, by poliovirus 3C proteinase. Expression of a cleavage-resistant G3BP restored SG formation during poliovirus infection and significantly inhibited virus replication. These results elucidate a mechanism for viral interference with mRNP metabolism and gene regulation and support a critical role of G3BP in SG formation and restriction of virus replication.
White
James P
JP
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Cardenas
Ana Maria
AM
Marissen
Wilfred E
WE
Lloyd
Richard E
RE
D000086042:3C Viral Proteases; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases; D005786:Gene Expression Regulation; D006801:Humans; D011051:Poliomyelitis / Q000378:metabolism* / Q000821:virology*; D017955:Poliovirus / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D014762:Viral Interference; D014764:Viral Proteins / Q000378:metabolism*
D002352:Carrier Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D014764:Viral Proteins; C026452:messenger ribonucleoprotein; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases