Abstract
Introduction. The efficacy of RNA interferon inducers depends not only on ligand structure and innate immune receptor engagement but also on the metabolic state of the target cell. Increasing evidence indicates that redox homeostasis, glutathione system parameters, mitochondrial functional reserve and antioxidant support influence the magnitude of interferon response, the balance between antiviral efficacy and inflammatory burden, and overall reproducibility of the effect. For yeast RNA-ascorbic acid complexes this issue is particularly important because ascorbate itself participates in redox regulation and may modify the molecular environment in which RNA-dependent immune activation occurs.
Objective. To systematize current data on the role of cellular redox status in shaping the response to RNA interferon inducers, to define the significance of the glutathione system, mitochondrial signaling and ascorbate-dependent mechanisms, and to propose a molecular model of personalized immunomodulation for yeast RNA and ascorbic acid complexes.
Material and methods. An analytical review of Russian and international publications devoted to pattern-recognition receptors for exogenous RNA, interferon response, redox homeostasis, glutathione system, mitochondrial signaling in innate immunity, biological effects of ascorbic acid, and molecular aspects of immunomodulatory RNA compositions was performed. The review included publications from PubMed, Scopus, Web of Science, eLibrary, as well as recent Russian works on yeast RNA, synergism of ascorbic acid and RNA interferon inducers, critical quality attributes of yeast ssRNA-ascorbate complexes, and their antiviral activity in vitro.
Basic Provisions. Cellular redox status was found to be one of the key determinants of the response to RNA interferon inducers. The most significant elements of this contour include the ratio of reduced to oxidized glutathione, the activity of glutathione peroxidase, superoxide dismutase and related antioxidant enzymes, as well as mitochondrial functional state and the MAVS signaling axis. Ascorbic acid may improve the reproducibility and completeness of response not only due to antioxidant effects, but also through modulation of epigenetic and enzyme-dependent mechanisms. A concept of redox-based stratification of efficacy of yeast RNA and ascorbic acid immunomodulatory complexes is proposed, involving simultaneous assessment of composition characteristics, baseline metabolic state of the cell and early interferon response markers.
Conclusion. For RNA interferon inducers, redox homeostasis should be considered a major molecular modifier of efficacy. In the case of yeast RNA-ascorbic acid complexes, the most promising strategy is transition to a personalized model of application that takes into account glutathione system parameters, mitochondrial reserve and antioxidant status. Integration of such markers into preclinical and early clinical-laboratory protocols may improve the predictability and molecular rationale of this platform.
Keywords
Authors and affiliations
https://elibrary.ru/hkzrtr
T.V. Potupchik(1), V.V. Ermolaev(2), S.V. Generalov(3), Yu.S. Alikin4, L.S. Evert(5), A.A. Tadevosian(6), Z.P. Metelkin(6), V.A. Popova(6(
1-Federal State Budgetary Educational Institution of Higher Education “Krasnoyarsk State Medical University named after Professor V.F. Voyno-Yasenetsky” of the Ministry of Health of the Russian Federation, Partizana Zheleznyaka St., 1, Krasnoyarsk, 660022, Russian Federation; 2-State Research Center
of Virology and Biotechnology “Vector” of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Koltsovo, Novosibirsk Region, 630559, Russian Federation; 3-Federal State Scientific Institution “Russian Anti-Plague Research Institute “Microbe” of the Federal Service
for Surveillance on Consumer Rights Protection and Human Wellbeing, Universitetskaya St., 46, Saratov, 410005, Russian Federation; 4-LLC “NPO Evolution of Nature”, Voskhod St., 20/1 premises 1.2, Novosibirsk, 630102, Russian Federation; 5-Federal State Budgetary Educational Institution of Higher Education “Khakass State University named after N.F. Katanov” of the Ministry of Science and Higher Education, 20/1 premises 1.2, Abakan, 20/1 premises 1.2, 655017, Russian Federation; 6-Federal State Autonomous Educational Institution of Higher Education “Russian National Research Medical University named after N.I. Pirogov” of the Ministry of Health of the Russian Federation, Ostrovityanova St., 1, building 6, Moscow, 117513, Russian Federation
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