title: Disruption of Stress Granule Formation by the Multifunctional Cricket Paralysis Virus 1A Protein.
abstract: Stress granules (SGs) are cytosolic ribonucleoprotein aggregates that are induced during cellular stress. Several viruses modulate SG formation, suggesting that SGs have an impact on virus infection. However, the mechanisms and impact of modulating SG assembly in infected cells are not completely understood. In this study, we identify the dicistrovirus cricket paralysis virus 1A (CrPV-1A) protein that functions to inhibit SG assembly during infection. Moreover, besides inhibiting RNA interference, CrPV-1A also inhibits host transcription, which indirectly modulates SG assembly. Thus, CrPV-1A is a multifunctional protein. We identify a key R146A residue that is responsible for these effects, and mutant CrPV(R146A) virus infection is attenuated inDrosophila melanogasterS2 cells and adult fruit flies and results in increased SG formation. Treatment of CrPV(R146A)-infected cells with actinomycin D, which represses transcription, restores SG assembly suppression and viral yield. In summary, CrPV-1A modulates several cellular processes to generate a cellular environment that promotes viral translation and replication.IMPORTANCERNA viruses encode a limited set of viral proteins to modulate an array of cellular processes in order to facilitate viral replication and inhibit antiviral defenses. In this study, we identified a viral protein, called CrPV-1A, within the dicistrovirus cricket paralysis virus that can inhibit host transcription, modulate viral translation, and block a cellular process called stress granule assembly. We also identified a specific amino acid within CrPV-1A that is important for these cellular processes and that mutant viruses containing mutations of CrPV-1A attenuate virus infection. We also demonstrate that the CrPV-1A protein can also modulate cellular processes in human cells, suggesting that the mode of action of CrPV-1A is conserved. We propose that CrPV-1A is a multifunctional, versatile protein that creates a cellular environment in virus-infected cells that permits productive virus infection.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Khong
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Craig H
authors.initials: CH
authors.lastname: Kerr
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Clarence H L
authors.initials: CHL
authors.lastname: Yeung
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Keatings
authors.affiliation: University of California-San Francisco, Department of Microbiology and Immunology, San Francisco, California, USA.
authors.forename: Arabinda
authors.initials: A
authors.lastname: Nayak
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Allan
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada ej@mail.ubc.ca.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0003-0523-8467
authors.initials: E
authors.lastname: Jan
mesh_terms: D000818:Animals; D003594:Cytoplasmic Granules / Q000502:physiology*; D004331:Drosophila melanogaster; D005260:Female; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D007304:Insect Viruses / Q000502:physiology*; D008297:Male; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000502:physiology*; D014779:Virus Replication
chemical_list: D014764:Viral Proteins
keywords: Drosophila; RNA; cricket paralysis virus; dicistrovirus; insect viruses; stress granules; transcription; translation; virus