In vitro immunomodulatory effect of siRNA complexes in the influenza infection

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Abstract

About 1.2 billion cases of influenza infection with up to 5 million cases of severe disease and up to 650,000 deaths from influenza and its complications are registered annually worldwide. High rates of morbidity and mortality are attributed to immunomodulatory properties of some proteins produced by the influenza viruses. Among these proteins, NS-1 is the most studied. One of its main functions is to disrupt the functioning of interferon-mediated defense mechanisms of the body thus causing suppressed production of different components of humoral immunity, which leads to an insufficiency of the immune response. It is known that miRNAs directed to cellular genes, which are involved in the process of viral reproduction, showing a pronounced antiviral activity. At the same time, only few studies have been focused on evaluation of their immunotropic effects. Therefore, the aim of our study was to quantify the concentrations of IFNα, IFNγ, TNFα and IL-10 cytokines as a result of complex suppression of the cellular FLT4, Nup98 and Nup205 gene activity, whose expression products play an important role in the reproduction of the influenza virus.

We have shown that the use of siRNA complexes also leads to an increase in the IFNα, IFNγ, TNFα and IL-10 concentrations. IL-10 production is absent on the first day after infection, but begins to increase on the second and third days. Moreover, in some cases, there is an increase in IFNα and IFNγ concentration on the first day after infection followed by decrease in their concentrations by the third day. This finding indicates that, upon supplement of the siRNA complexes, the cytokine profile is normalized under the influence of IL-10.

About the authors

Evgeny A. Pashkov

I. Mechnikov Research Institute of Vaccines and Sera; I. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: pashckov.j@yandex.ru
ORCID iD: 0000-0002-5682-4581

Junior Research Associate, Laboratory of Molecular Immunology, I. Mechnikov Research Institute of Vaccines and Sera; Assistant Professor, Department of Microbiology, Virology and Immunology, I. Sechenov First Moscow State Medical University

Russian Federation, Moscow; Moscow

R. V. Samoilikov

I. Mechnikov Research Institute of Vaccines and Sera

Email: roma_sam78@mail.ru

Research Associate, Laboratory of Molecular Immunology, I. Sechenov First Moscow State Medical University

Russian Federation, Moscow

G. A. Pryanikov

I. Sechenov First Moscow State Medical University (Sechenov University)

Email: 8230712@mail.ru

Postgraduate Student, Department of Epidemiology and Evidence-based Medicine, I. Sechenov First Moscow State Medical University (Sechenov University)

Russian Federation, Moscow

A. S. Bykov

I. Sechenov First Moscow State Medical University (Sechenov University)

Email: bykov_a_s@staff.sechenov.ru

PhD, MD (Medicine), Professor, Department of Microbiology, Virology and Immunology, I. Sechenov First Moscow State Medical University (Sechenov University)

Russian Federation, Moscow

E. P. Pashkov

I. Sechenov First Moscow State Medical University (Sechenov University)

Email: 8230712@mail.ru

PhD, MD (Medicine), Professor, Department of Microbiology, Virology and Immunology, I. Sechenov First Moscow State Medical University (Sechenov University)

Russian Federation, Moscow

A. V. Poddubikov

I. Mechnikov Research Institute of Vaccines and Sera

Email: poddubikov@yandex.ru

PhD (Biology), Head, Laboratory of Microbiology of Opportunistic Bacteria, I. Mechnikov Research Institute of Vaccines and Sera

Russian Federation, Moscow

O. A. Svitich

I. Mechnikov Research Institute of Vaccines and Sera; I. Sechenov First Moscow State Medical University (Sechenov University)

Email: svitichoa@yandex.ru

PhD, MD (Medicine), Corresponding Member, Russian Academy of Sciences, Director, I. Mechnikov Research Institute of Vaccines and Sera; Professor, Department of Microbiology, Virology and Immunology, I. Sechenov First Moscow State Medical University (Sechenov University)

Russian Federation, Moscow; Moscow

V. V. Zverev

I. Mechnikov Research Institute of Vaccines and Sera; I. Sechenov First Moscow State Medical University (Sechenov University)

Email: vitalyzverev@outlook.com

PhD, MD (Biology), Full Member, Russian Academy of Sciences, Scientific Advisor, I. Mechnikov Research Institute of Vaccines and Sera; Professor, Department of Microbiology, Virology and Immunology, I. Sechenov First Moscow State Medical University (Sechenov University)

Russian Federation, Moscow; Moscow

References

  1. Пашков Е.А., Пак А.В., Абрамова Н.Д., Яковлева И.В., Вартанова Н.О., Богданова Е.А., Пашков Е.П., Свитич О.А., Зверев В.В. Изучение экспрессии гена IL-1β под действием комплексов миРНК, обладающих противогриппозным действием // Российский иммунологический журнал, 2022. № 4. C. 485-490. [Pashkov E.A., Pak A.V., Abramova N.D., Yakovleva I.V., Vartanova N.O., Bogdanova E.A., Pashkov E.P., Svitich O.A., Zverev V.V. Studying expression of IL-1β gene under the action of siRNA complexes with anti-influenza effect. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2022, Vol. 25, no. 4, pp. 485-490. (In Russ.)] doi: 10.46235/1028-7221-1202-SEO.
  2. Fong C., Lu L., Chen L., Yeung M., Zhang A., Zhao H., Yuen K., To K. Interferon-gamma inhibits influenza A virus cellular attachment by reducing sialic acid cluster size. iScience, 2022, Vol. 25, no. 4, pp. 1-27.
  3. Hayden M., Ghosh S. Shared principles in NF-kappaB signaling. Cell, 2008, Vol. 132, no. 4, pp. 344-362.
  4. Hou Y., Wang Y., Chen J., Chen C. Dual roles of tumor necrosis factor superfamily 14 in antiviral immunity. Viral Immunol., 2022, Vol. 35, no. 9, pp. 579-585.
  5. Jordan S. Innate and adaptive immune responses to SARS-CoV-2 in humans: relevance to acquired immunity and vaccine responses. Clin. Exp. Immunol., 2021. Vol. 204, no. 3, pp. 310-320.
  6. Lampejo T. Influenza and antiviral resistance: an overview. Eur. J. Clin. Microbiol. Infect. Dis., 2020, Vol. 39, no. 7, pp. 1201-1208.
  7. Matikainen S., Paananen A., Miettinen M., Kurimoto M., Timonen T., Julkunen I., Sareneva T. IFN-alpha and IL-18 synergistically enhance IFN-gamma production in human NK cells: differential regulation of Stat4 activation and IFN-gamma gene expression by IFN-alpha and IL-12. Eur. J. Immunol., 2001, Vol. 31, no. 7, pp. 2236-2245.
  8. Plotnikova M., Klotchenko S., Vasin A. Development of a multiplex quantitative PCR assay for the analysis of human cytokine gene expression in influenza A virus-infected cell. J. Immunol. Methods, 2016, Vol. 430, pp. 51-55.
  9. Sareneva T., Matikainen S., Kurimoto M., Julkunen I. Influenza A virus-induced IFN-alpha/beta and IL-18 synergistically enhance IFN-gamma gene expression in human T cells. J. Immunol., 1998, Vol. 160, no. 12, pp. 6032-6038.
  10. Wang X., Wong K., Ouyang W., Rutz S. Targeting IL-10 Family Cytokines for the Treatment of Human Diseases. Cold Spring Harb. Perspect. Biol., 2019, Vol. 11, no. 2, a028548. doi: 10.1101/cshperspect.a028548.

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2. Figure 1. Effect of siRNA complexes directed to the FLT4, Nup98 and Nup205 genes on the change in IL-10 concentration with a multiplicity of infection = 0.01 (*, p ≤ 0.05)

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3. Figure 2. Effect of siRNA complexes directed to the FLT4, Nup98 and Nup205 genes on the change in IL-10 concentration with a multiplicity of infection = 0.01 (*, p ≤ 0.05)

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Copyright (c) 2023 Pashkov E.A., Samoilikov R.V., Pryanikov G.A., Bykov A.S., Pashkov E.P., Poddubikov A.V., Svitich O.A., Zverev V.V.

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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