title: Modulation of stress granules and P bodies during dicistrovirus infection.
abstract: Stress granules (SGs) are dynamic cytosolic aggregates composed of ribonucleoproteins that are induced during cellular stress when protein synthesis is inhibited. The function of SGs is poorly understood, but they are thought to be sites for reorganizing mRNA and protein. Several viruses can modulate SG formation, suggesting that SGs have an impact on virus infection. In this study, we have investigated the relationship of SG formation in Drosophila S2 cells infected by cricket paralysis virus (CrPV), a member of the Dicistroviridae family. Despite a rapid shutoff of host translation during CrPV infection, several hallmark SG markers such as the Drosophila TIA-1 and G3BP (RasGAP-SH3-binding protein) homologs, Rox8 and Rin, respectively, do not aggregate in CrPV-infected cells, even when challenged with potent SG inducers such as heat shock, oxidative stress, and pateamine A treatment. Furthermore, we demonstrate that a subset of P body markers become moderately dispersed at late times of infection. In contrast, as shown by fluorescent in situ hybridization, poly(A)(+) RNA granules still form at late times of infection. These poly(A)(+) RNA granules do not contain viral RNA nor do they colocalize with P body markers. Finally, our results demonstrate that the CrPV viral 3C protease is sequestered to SGs under cellular stress but not during virus infection. In summary, we propose that dicistrovirus infection leads to the selective inhibition of distinct SGs so that viral proteins are available for viral processing.
authors.affiliation: Department of Biochemistry and Molecular Biology, 5457-2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Khong
authors.forename: Eric
authors.initials: E
authors.lastname: Jan
mesh_terms: D000086042:3C Viral Proteases; D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000378:metabolism*; D056629:Dicistroviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004330:Drosophila / Q000166:cytology / Q000821:virology; D005786:Gene Expression Regulation; D018869:Heat-Shock Response; D011132:Polyribosomes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012367:RNA, Viral; D012261:Ribonucleoproteins; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases