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Dual Effect of Organogermanium Compound THGP on RIG-I-Mediated Viral Sensing and Viral Replication during Influenza a Virus Infection

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Title: Dual Effect of Organogermanium Compound THGP on RIG-I-Mediated Viral Sensing and Viral Replication during Influenza a Virus Infection
Authors: Baidya, Sunanda Browse this author
Nishimoto, Yoko Browse this author
Sato, Seiichi Browse this author →KAKEN DB
Shimada, Yasuhiro Browse this author
Sakurai, Nozomi Browse this author
Nonaka, Hirotaka Browse this author
Noguchi, Koki Browse this author
Kido, Mizuki Browse this author
Tadano, Satoshi Browse this author
Ishikawa, Kozo Browse this author →KAKEN DB
Li, Kai Browse this author
Okubo, Aoi Browse this author
Yamada, Taisho Browse this author →KAKEN DB
Orba, Yasuko Browse this author →KAKEN DB
Sasaki, Michihito Browse this author →KAKEN DB
Sawa, Hirofumi Browse this author →KAKEN DB
Miyamoto, Hiroko Browse this author
Takada, Ayato Browse this author →KAKEN DB
Nakamura, Takashi Browse this author →KAKEN DB
Takaoka, Akinori Browse this author →KAKEN DB
Keywords: influenza a virus
viral replication
recognition of 5 '-triphosphate RNA
antiviral agent
Issue Date: Sep-2021
Publisher: MDPI
Journal Title: Viruses-Basel
Volume: 13
Issue: 9
Start Page: 1674
Publisher DOI: 10.3390/v13091674
Abstract: 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.
Type: article
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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