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- Title
Critical Role of an Antiviral Stress Granule Containing RIG-I and PKR in Viral Detection and Innate Immunity.
- Authors
Onomoto, Koji; Jogi, Michihiko; Yoo, Ji-Seung; Narita, Ryo; Morimoto, Shiho; Takemura, Azumi; Sambhara, Suryaprakash; Kawaguchi, Atushi; Osari, Suguru; Nagata, Kyosuke; Matsumiya, Tomoh; Namiki, Hideo; Yoneyama, Mitsutoshi; Fujita, Takashi; Kanai, Akio
- Abstract
Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) function as cytoplasmic sensors for viral RNA to initiate antiviral responses including type I interferon (IFN) production. It has been unclear how RIG-I encounters and senses viral RNA. To address this issue, we examined intracellular localization of RIG-I in response to viral infection using newly generated anti- RIG-I antibody. Immunohistochemical analysis revealed that RLRs localized in virus- induced granules containing stress granule (SG) markers together with viral RNA and antiviral proteins. Because of similarity in morphology and components, we termed these aggregates antiviral stress granules (avSGs). Influenza A virus (IAV) deficient in non-structural protein 1 (NS1) efficiently generated avSGs as well as IFN, however IAV encoding NS1 produced little. Inhibition of avSGs formation by removal of either the SG component or double-stranded RNA (dsRNA)- dependent protein kinase (PKR) resulted in diminished IFN production and concomitant enhancement of viral replication. Furthermore, we observed that transfection of dsRNA resulted in IFN production in an avSGs-dependent manner. These results strongly suggest that the avSG is the locus for non-self RNA sensing and the orchestration of multiple proteins is critical in the triggering of antiviral responses.
- Subjects
TRETINOIN; RNA; INTERFERON inducers; VIRUS diseases; IMMUNOHISTOCHEMISTRY; MORPHOLOGY; GENE transfection
- Publication
PLoS ONE, 2012, Vol 7, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0043031