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タイトル	en Dual Effect of Organogermanium Compound THGP on RIG-I-Mediated Viral Sensing and Viral Replication during Influenza a Virus Infection
作成者	en Baidya, Sunanda en Nishimoto, Yoko en Sato, Seiichi NRID 1000060459724 en Shimada, Yasuhiro en Sakurai, Nozomi en Nonaka, Hirotaka en Noguchi, Koki en Kido, Mizuki en Tadano, Satoshi en Ishikawa, Kozo NRID 1000020624795 en Li, Kai en Okubo, Aoi en Yamada, Taisho NRID 1000010779333 en Orba, Yasuko NRID 1000060507169 en Sasaki, Michihito NRID 1000070609403 en Sawa, Hirofumi NRID 1000030292006 en Miyamoto, Hiroko en Takada, Ayato NRID 1000010292062 en Nakamura, Takashi NRID 1000020604458 en Takaoka, Akinori NRID 1000030323611
アクセス権	metadata only access
主題	Other en influenza a virus Other en viral replication Other en recognition of 5 '-triphosphate RNA Other en antiviral agent Other en THGP Other en RIG-I NDC 490
内容注記	Abstract en The interaction of viral nucleic acid with protein factors is a crucial process for initiating viral polymerase-mediated viral genome replication while activating pattern recognition receptor (PRR)-mediated innate immune responses. It has previously been reported that a hydrolysate of Ge-132, 3-(trihydroxygermyl) propanoic acid (THGP), shows a modulatory effect on microbial infections, inflammation, and immune responses. However, the detailed mechanism by which THGP can modify these processes during viral infections remained unknown. Here, we show that THGP can specifically downregulate type I interferon (IFN) production in response to stimulation with a cytosolic RNA sensor RIG-I ligand 5 '-triphosphate RNA (3pRNA) but not double-stranded RNA, DNA, or lipopolysaccharide. Consistently, treatment with THGP resulted in the dose-dependent suppression of type I IFN induction upon infections with influenza virus (IAV) and vesicular stomatitis virus, which are known to be mainly sensed by RIG-I. Mechanistically, THGP directly binds to the 5 '-triphosphate moiety of viral RNA and competes with RIG-I-mediated recognition. Furthermore, we found that THGP can directly counteract the replication of IAV but not EMCV (encephalitismyocarditis virus), by inhibiting the interaction of viral polymerase with RNA genome. Finally, IAV RNA levels were significantly reduced in the lung tissues of THGP-treated mice when compared with untreated mice. These results suggest a possible therapeutic implication of THGP and show direct antiviral action, together with the suppressive activity of innate inflammation.
出版者	en MDPI
日付	Issued2021-09
言語	eng
資源タイプ	journal article
出版タイプ	NA
資源識別子	HDL http://hdl.handle.net/2115/83165
関連	isIdenticalTo DOI https://doi.org/10.3390/v13091674
収録誌情報	en Viruses-Basel 巻13 号9 開始ページ1674
コンテンツ更新日時	2023-07-26