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Title
  • en Dual Effect of Organogermanium Compound THGP on RIG-I-Mediated Viral Sensing and Viral Replication during Influenza a Virus Infection
Creator
Accessrights metadata only access
Subject
  • 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
Description
  • 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.
Publisher en MDPI
Date
    Issued2021-09
Language
  • eng
Resource Type journal article
Version Type NA
Identifier HDL http://hdl.handle.net/2115/83165
Relation
  • isIdenticalTo DOI https://doi.org/10.3390/v13091674
Journal
  • en Viruses-Basel
  • Volume Number13 Issue Number9 Page Start1674
Oaidate 2023-07-26