title: Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.
abstract: Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection.
authors: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Shin
authors: S
authors: Hashimoto
authors: Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Soh
authors: S
authors: Yamamoto
authors: Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Otorhinolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Noriko
authors: N
authors: Ogasawara
authors: Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Toyotaka
authors: T
authors: Sato
authors: Department of Otorhinolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Keisuke
authors: K
authors: Yamamoto
authors: Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Katoh
authors: Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
authors: Toru
authors: T
authors: Kubota
authors: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Tsukasa
authors: T
authors: Shiraishi
authors: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Takashi
authors: T
authors: Kojima
authors: Department of Otorhinolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Tetsuo
authors: T
authors: Himi
authors: Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Hiroyuki
authors: H
authors: Tsutsumi
authors: Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors: Shin-Ichi
authors: S
authors: Yokota
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D002522:Chlorocebus aethiops; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000821:virology*; D000071457:DEAD Box Protein 58 / Q000378:metabolism; D004265:DNA Helicases; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007372:Interferons / Q000096:biosynthesis* / Q000235:genetics; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D009109:Mumps virus / Q000502:physiology*; D039102:Poly(A)-Binding Proteins / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D034622:RNA Interference; D000067776:RNA Recognition Motif Proteins; D011971:Receptors, Immunologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013312:Stress, Physiological / Q000502:physiology; D000074019:T-Cell Intracellular Antigen-1; D014709:Vero Cells; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D039102:Poly(A)-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D011971:Receptors, Immunologic; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D007372:Interferons; D019892:eIF-2 Kinase; C452820:RIGI protein, human; D004265:DNA Helicases; C116070:G3BP1 protein, human; D000071457:DEAD Box Protein 58; D020365:RNA Helicases