Viruses, 2021-08, Vol.13 (9), p.1674
2021
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- Autor(en) / Beteiligte
- Titel
- Dual Effect of Organogermanium Compound THGP on RIG-I-Mediated Viral Sensing and Viral Replication during Influenza a Virus Infection
- Ist Teil von
- Viruses, 2021-08, Vol.13 (9), p.1674
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1999-4915eISSN: 1999-4915DOI: 10.3390/v13091674Titel-ID: cdi_doaj_primary_oai_doaj_org_article_4e2449946abf498b97e0e2579d34aa5c
- Format
- –
- Schlagworte
- A549 Cells, Animals, Antibodies, Antiviral activity, antiviral agent, Antiviral Agents - metabolism, Antiviral Agents - pharmacology, Antiviral Agents - therapeutic use, DNA-directed RNA polymerase, Double-stranded RNA, Genomes, Hepatitis, Host-Pathogen Interactions - drug effects, Humans, Hydrolysates, Immune response, Immunity, Innate - drug effects, Infections, Infectious diseases, Inflammation, Influenza, Influenza A, influenza a virus, Influenza A virus - immunology, Influenza A virus - pathogenicity, Influenza A virus - physiology, Innate immunity, Interferon, Interferon Type I - immunology, Interferon Type I - metabolism, Ligands, Lipopolysaccharides, Mice, Organometallic Compounds - metabolism, Organometallic Compounds - pharmacology, Organometallic Compounds - therapeutic use, Orthomyxoviridae Infections - drug therapy, Orthomyxoviridae Infections - immunology, Orthomyxoviridae Infections - virology, Pattern recognition receptors, Plasmids, Propionic acid, Proteins, RAW 264.7 Cells, Reagents, Receptors, Retinoic Acid - genetics, Receptors, Retinoic Acid - immunology, recognition of 5′-triphosphate RNA, Replication, RIG-I, RNA polymerase, RNA, Viral - genetics, RNA, Viral - metabolism, Sensors, Severe acute respiratory syndrome coronavirus 2, Stomatitis, THGP, Viral infections, Viral Nonstructural Proteins - genetics, Viral Nonstructural Proteins - metabolism, viral replication, Virus Replication - drug effects, Virus Replication - genetics, Viruses