Complexes of Oligoribonucleotides with d-Mannitol Modulate the Innate Immune Response to Influenza A Virus H1N1 (A/FM/1/47) In Vivo

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 11; no. 3; p. 73
• Main Authors: Melnichuk, Nataliia, Kashuba, Vladimir, Rybalko, Svitlana, Tkachuk, Zenoviy
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-07-2018; MDPI
• Subjects: Chemokines; Drug resistance; Gene expression; Infections; Inflammation; Influenza; Kinases; Lipid peroxidation; Lipids; Lungs; Medicin och hälsovetenskap; oligoribonucleotides-d-mannitol complexes; Prevention; pro-inflammatory immune responses; Proteins; Viruses; Ukraine; influenza; oligoribonucleotides-d-mannitol complexes; pro-inflammatory immune responses
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph11030073

Rapid replication of the influenza A virus and lung tissue damage caused by exaggerated pro-inflammatory host immune responses lead to numerous deaths. Therefore, novel therapeutic agents that have anti-influenza activities and attenuate excessive pro-inflammatory responses that are induced by an influenza virus infection are needed. Oligoribonucleotides-d-mannitol (ORNs-d-M) complexes possess both antiviral and anti-inflammatory activities. The current research was aimed at studying the ORNs-d-M effects on expression of innate immune genes in mice lungs during an influenza virus infection. Expression of genes was determined by RT-qPCR and Western blot assays. In the present studies, we found that the ORNs-d-M reduced the influenza-induced up-expression of Toll-like receptors (TLRs) (
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), nuclear factor NF-kB (
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), cytokines (
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), chemokines (
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), interferon-stimulated genes (ISGs) (
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), and pro-oxidation (
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) genes. The ORNs-d-M inhibited the mRNA overexpression of
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, and
induced by the influenza virus, which suggests that they impair the upregulation of NF-kB, cytokines, chemokines, ISGs, and pro-oxidation genes induced by the influenza virus by inhibiting activation of the TLR-3, TLR-7, and TLR-8 signaling pathways. By impairing activation of the TLR-3, TLR-7, and TLR-8 signaling pathways, the ORNs-d-M can modulate the innate immune response to an influenza virus infection.