The Mechanism of Suppression of Chronic Hepatitis C Infection by the Medicine Stimforte
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BIOLOGY
The Mechanism of Suppression of Chronic Hepatitis C Infection by the Medicine Stimforte D. V. Mishina, E. I. Isaevaa, S. S. Grigorianb, A. A. Balakinac, A. V. Ilyichevd, P. G. Deryabina, †, and D. G. Maldovd, * aFederal
State Budgetary Institution Gamaleya Federal Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation (Ivanovskii Institute of Virology), Moscow, 123098 Russia bFederal State Budgetary Institution Gamaleya Federal Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation (Gamalei Institute of Epidemiology and Microbiology), Moscow, 123098 Russia c Federal State Budgetary Institution Institute of Problems of Chemical Physics, Russian Academy of Sciences, Moscow oblast, 142432 Russia dZAO SKY Limited, Moscow, 129301 Russia *e-mail: [email protected] Received September 17, 2017; revised March 5, 2019; accepted December 13, 2019
Abstract—The effect of the drug Stimforte on infection by the Hepatitis C virus (HCV) has been studied. Stimforte partially inhibits HCV infection at a dose of 100 μg/mouse and almost completely at a dose of 300 μg/mouse within 24 h after administration of the drug. The mice sera resulting after 24 h in the presence of 100 and 300 μg/mouse of Stimforte effectively inhibit the production of HCV. Doses of 150, 200, and 250 μg/mouse are not effective. Stimulation of interferon-β (IFN-β) production is only observed at doses of 100 and 300 μg/mouse, which explains well the neutralizing capacity of the sera. The amount of IFN-γ also correlates well with the antiviral activity and neutralizing activity of mice sera. The drug practically does not stimulate production of IFN-λ. Thus, the neutralizing activity of sera and the antiviral activity are largely determined by the 1st and 2nd IFN groups. DOI: 10.1134/S1062359020050076
INTRODUCTION Hepatitis C is related to indicators of social and medical well-being in society. Worldwide, the hepatitis C virus (HCV) infects ~3% of the population (170– 180 million people), which is five times higher than the prevalence of the human immunodeficiency virus. The absence of protective immunity after acute hepatitis C and the absence of a vaccine against this virus make particularly relevant the search for the mechanisms by which the virus avoids the identification and elimination of neutralizing antibodies and cells of the immune system that also inhibit the development of this infection. Earlier, we discovered the effect of the drug Stimforte on chronic HCV infection in mice (Deryabin et al., 2009) and that it belongs to the group of immunostimulants that activate the immune system primarily through the toll-like receptor 4 (TLR-4) (Maldov et al., 2011). The mechanism of action of any drug also largely determines the scope of its use. Moreover, the viral infection itself significantly modulates the effect of immunomodulating agents, since, on the one hand, viruses cause a cell response the host’s immune system † Deceased.
and target cells and, on the other han
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