Alteration of IFNα and IFNβ gene expression by siRNA targeting the Nup98 gene during in vitro HSV-1 infection
- Authors: Pashkov E.A.1,2, Kulikova L.A.1,2, Svitich O.A.1,2, Zverev V.V.1,2
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Affiliations:
- I. Mechnikov Research Institute for Vaccines and Sera
- I. Sechenov First Moscow State Medical University (Sechenov University)
- Issue: Vol 28, No 4 (2025)
- Pages: 925-930
- Section: SHORT COMMUNICATIONS
- URL: https://journals.rcsi.science/1028-7221/article/view/333252
- DOI: https://doi.org/10.46235/1028-7221-17254-AOI
- ID: 333252
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Abstract
Herpes simplex virus type 1 (HSV-1) is taxonomically classified as α-herpesvirus and is a complex double-stranded DNA virus. HSV-1 infections are extremely common among human population, with a global prevalence of 65% in persons under 50. In addition to labial and genital lesions, HSV-1-associated diseases include herpetic stromal keratitis, HSV encephalitis, and Alzheimer’s disease. Therefore, adaptive immune response is essential for controlling HSV infection, its reactivation, and complications. Key components of the adaptive immunity include IFNα and IFNβ, which play an important role at the early stages of infection caused by herpesviruses. Increased IFNα expression induces a systemic immune response, by activating NK cells, T lymphocytes, and increasing their migration to the inflammation site, as well as suppression of the viral life cycle by stimulating NK cell cytotoxicity and Th1 cell differentiation. Moreover, the main functions of IFNβ are to induce expression of interferon-stimulating genes (ISGs), whose expression products are able to inhibit viral reproduction cycle at various stages. A wide range of drug therapies and other approaches are currently used to treat herpes infections. Over time, however, an increased incidence of HSV-1 infection is observed in general population. In view of the current trends, it is necessary to search for new approaches aimed at reducing the incidence of HSV-1 infection and its complications. A promising approach may include usage of RNA interference effect, which underlies the action of potential new-generation antiherpetic drugs. RNA interference is a targeted inhibition of mRNA translation which entails disruption of subsequent protein biosynthesis. During its reproduction, HSV-1 imports viral DNA through the nuclear pore complex (NPC), located at the nuclear membrane. The NPC consists of nucleoporin proteins (Nup98, Nup205, NXF1 and others). Therefore, disruption of NPC structure resulting from miRNA-mediated inhibition of nucleoporin protein formation may hypothetically lead to a decreased HSV-1 reproduction.
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##article.viewOnOriginalSite##About the authors
Evgeny A. Pashkov
I. Mechnikov Research Institute for 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
PhD (Medicine), Junior Researcher, Laboratory of Molecular Immunology, Senior Lecturer, Department of Microbiology, Virology and Immunology, F. Erisman Institute of Public Health
Russian Federation, 5a Maly Kazenny Lane, Moscow, 105064; MoscowLiana A. Kulikova
I. Mechnikov Research Institute for Vaccines and Sera; I. Sechenov First Moscow State Medical University (Sechenov University)
Email: LianaKulikovaMira@yandex.ru
ORCID iD: 0009-0005-0203-1382
Student, Laboratory Assistant, Laboratory of Molecular Immunology
Russian Federation, 5a Maly Kazenny Lane, Moscow, 105064; MoscowOxana A. Svitich
I. Mechnikov Research Institute for Vaccines and Sera; I. Sechenov First Moscow State Medical University (Sechenov University)
Email: svitichoa@yandex.ru
ORCID iD: 0000-0003-1757-8389
PhD, MD (Medicine), Corresponding Member, Russian Academy of Sciences, Head, Laboratory of Molecular Immunology, Director, Professor, Department of Microbiology, Virology and Immunology
Russian Federation, 5a Maly Kazenny Lane, Moscow, 105064; MoscowVytaly V. Zverev
I. Mechnikov Research Institute for Vaccines and Sera; I. Sechenov First Moscow State Medical University (Sechenov University)
Email: vitalyzverev@outlook.com
ORCID iD: 0000-0002-0017-1892
PhD, MD (Biology), Full Member, Russian Academy of Sciences, Scientific Advisor, Professor, Head. Department of Microbiology, Virology and Immunology
Russian Federation, 5a Maly Kazenny Lane, Moscow, 105064; MoscowReferences
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