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

1
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03680 Kyiv, Ukraine
2
Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, S-17177 Stockholm, Sweden
3
Gromashevsky L. V. Institute of Epidemiology and Infectious Diseases, NAMSU, 5 Amosov str., 03038 Kyiv, Ukraine
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2018, 11(3), 73; https://doi.org/10.3390/ph11030073
Received: 19 June 2018 / Revised: 18 July 2018 / Accepted: 18 July 2018 / Published: 22 July 2018
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) (tlr3, tlr7, tlr8), nuclear factor NF-kB (nfkbia, nfnb1), cytokines (ifnε, ifnk, ifna2, ifnb1, ifnγ, il6, il1b, il12a, tnf), chemokines (ccl3, ccl4, сcl5, cxcl9, cxcl10, cxcl11), interferon-stimulated genes (ISGs) (oas1a, oas2, oas3, mx1), and pro-oxidation (nos2, xdh) genes. The ORNs-d-M inhibited the mRNA overexpression of tlr3, tlr7, and tlr8 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. View Full-Text
Keywords: oligoribonucleotides-d-mannitol complexes; influenza; pro-inflammatory immune responses oligoribonucleotides-d-mannitol complexes; influenza; pro-inflammatory immune responses
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Melnichuk, N.; Kashuba, V.; Rybalko, S.; Tkachuk, Z. Complexes of Oligoribonucleotides with d-Mannitol Modulate the Innate Immune Response to Influenza A Virus H1N1 (A/FM/1/47) In Vivo. Pharmaceuticals 2018, 11, 73.

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