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  • Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity.

Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity.

PloS one (2012-08-23)
Koji Onomoto, Michihiko Jogi, Ji-Seung Yoo, Ryo Narita, Shiho Morimoto, Azumi Takemura, Suryaprakash Sambhara, Atushi Kawaguchi, Suguru Osari, Kyosuke Nagata, Tomoh Matsumiya, Hideo Namiki, Mitsutoshi Yoneyama, Takashi Fujita
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.

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Anti-Actin Antibody, clone C4, clone C4, Chemicon®, from mouse