| 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 |
| THGP |
| RIG-I |
| 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 |
| URI: | http://hdl.handle.net/2115/83165 |
| 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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