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Dual Effect of Organogermanium Compound THGP on RIG-I-Mediated Viral Sensing and Viral Replication during Influenza a Virus Infection.
- Source :
-
Viruses [Viruses] 2021 Aug 24; Vol. 13 (9). Date of Electronic Publication: 2021 Aug 24. - Publication Year :
- 2021
-
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.
- Subjects :
- A549 Cells
Animals
Antiviral Agents metabolism
Antiviral Agents therapeutic use
Host-Pathogen Interactions drug effects
Humans
Influenza A virus immunology
Influenza A virus pathogenicity
Interferon Type I immunology
Interferon Type I metabolism
Mice
Organometallic Compounds metabolism
Organometallic Compounds therapeutic use
Orthomyxoviridae Infections drug therapy
Orthomyxoviridae Infections immunology
Orthomyxoviridae Infections virology
RAW 264.7 Cells
RNA, Viral genetics
RNA, Viral metabolism
Receptors, Retinoic Acid immunology
Viral Nonstructural Proteins metabolism
Virus Replication genetics
Antiviral Agents pharmacology
Immunity, Innate drug effects
Influenza A virus physiology
Organometallic Compounds pharmacology
Receptors, Retinoic Acid genetics
Viral Nonstructural Proteins genetics
Virus Replication drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 13
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 34578256
- Full Text :
- https://doi.org/10.3390/v13091674