Problems of VirologyProblems of VirologyВопросы вирусологии0507-40882411-2097Central Research Institute for Epidemiology1671210.36233/0507-4088-289oqonmmORIGINAL RESEARCHESОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯResearch ArticleAssessment of the preventive effect of knockdown of cellular genes NXF1, PRPS1PRPS1 and NAA10 in influenza infection in an in vitro modelОценка профилактического эффекта нокдауна клеточных генов NXF1, PRPS1 и NAA10 при гриппозной инфекции на модели in vitrohttps://orcid.org/0000-0002-5682-4581PashkovEvgeny A.ПашковЕвгений Алексеевич
Russian Federation

Ph. D., assistant of microbiology, virology and immunology department of Sechenov University; junior researcher laboratory of virology applied of I. Mechnikov Research Institute of Vaccines and Sera

канд. мед. наук, ассистент кафедры микробиологии, вирусологии и иммунологии ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет); младший научный сотрудник лаборатории прикладной вирусологии ФГБНУ НИИВС им. И.И. Мечникова

pashckov.j@yandex.ruhttps://orcid.org/0009-0005-9874-2081ShikvinDmitry A.ШиквинДмитрий Андреевич
Russian Federation

student of the Department of Biotechnology and Industrial Pharmacy of the Institute of Fine Chemical Technologies named after M.V. Lomonosov

студент кафедры биотехнологии и промышленной фармации института тонких химических технологий им. М.В. Ломоносова

carrypool@gmail.comhttps://orcid.org/0000-0003-0392-9969PashkovGeorge A.ПашковГеоргий Алексеевич
Russian Federation

student of the Institute of Children Health

студент клинического института детского здоровья им. Н.Ф. Филатова

georgp2004@mail.ruhttps://orcid.org/0000-0001-8204-4899NagievaFiraya G.НагиеваФирая Галиевна
Russian Federation

MD, private-docent, The Head of laboratory of hybrid cell cultures

д-р мед. наук, доцент, заведующая лабораторией гибридных клеточных культур

fgn42@yandex.ruhttps://orcid.org/0000-0002-5620-1843BogdanovaEkaterina A.БогдановаЕкатерина Александровна
Russian Federation

Ph. D., private-docent of Microbiology, Virology and Immunology department

канд. мед. наук, доцент кафедры микробиологии, вирусологии и иммунологии

bogdekaterin@yandex.ruhttps://orcid.org/0000-0002-8099-6201BykovAnatoly S.БыковАнатолий Сергеевич
Russian Federation

MD, Professor of Microbiology, Virology and Immunology department

д-р мед. наук, профессор кафедры микробиологии, вирусологии и иммунологии

drbykov@bk.ruhttps://orcid.org/0000-0002-4963-5053PashkovEvgeny P.ПашковЕвгений Петрович
Russian Federation

MD, Professor of Microbiology, Virology and Immunology department

д-р мед. наук, профессор кафедры микробиологии, вирусологии и иммунологии

9153183256@mail.ruhttps://orcid.org/0000-0003-1757-8389SvitichOxana A.СвитичОксана Анатольевна
Russian Federation

Corresponding member of RAS, MD, The head of I. Mechnikov Research Institute of Vaccines and Sera; Professor of Microbiology, Virology and Immunology department of Sechenov University

чл.-корр. РАН, д-р мед. наук, директор ФГБНУ НИИВС им И.И. Мечникова, заведующая лабораторией молекулярной иммунологии ФГБНУ НИИВС им. И.И. Мечникова, профессор кафедры микробиологии, вирусологии и иммунологии ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)

svitichoa@yandex.ruhttps://orcid.org/0000-0002-0017-1892ZverevVitaly V.ЗверевВиталий Васильевич
Russian Federation

Academician of RAS, Doctor of Biological Sciences, Scientific Adviser of I. Mechnikov Research Institute of Vaccines and Sera; Professor, The Leader of Microbiology, Virology and Immunology department of Sechenov University

академик РАН, д-р биол. наук, научный руководитель ФГБНУ НИИВС им. И.И. Мечникова, профессор, заведующий кафедрой микробиологии, вирусологии и иммунологии ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Сеченовский Университет)

vitalyzverev@outlook.comSechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)ФГБУН «Научно-исследовательский институт вакцин и сывороток им. И.И. Мечникова» Минздрава РоссииI.I. Mechnikov Scientific and Research Institute of Vaccines and SeraФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)Moscow State University of Fine Chemical TechnologiesФГБОУ ВО «МИРЭА – Российский технологический университет»12032025701667715012025Copyright ©; 2025, Pashkov E.A., Shikvin D.A., Pashkov G.A., Nagieva F.G., Bogdanova E.A., Bykov A.S., Pashkov E.P., Svitich O.A., Zverev V.V.Copyright ©; 2025, Пашков Е.А., Шиквин Д.А., Пашков Г.А., Нагиева Ф.Г., Богданова Е.А., Быков А.С., Пашков Е.П., Свитич О.А., Зверев В.В.2025Pashkov E.A., Shikvin D.A., Pashkov G.A., Nagieva F.G., Bogdanova E.A., Bykov A.S., Pashkov E.P., Svitich O.A., Zverev V.V.Пашков Е.А., Шиквин Д.А., Пашков Г.А., Нагиева Ф.Г., Богданова Е.А., Быков А.С., Пашков Е.П., Свитич О.А., Зверев В.В.https://creativecommons.org/licenses/by/4.0https://virusjour.crie.ru/jour/article/view/16712

Introduction. Influenza is an acute respiratory viral infectious disease caused by the influenza viruses. Current preventive and therapeutic approaches are of great anti-epidemic importance, but there are a number of problems, such as the rapid emergence of resistant strains, the lack of cross-immunity and the effectiveness of vaccines. One of the approaches to the development of anti-influenza agents is the use of RNA interference and small interfering RNAs complementary to the mRNA target of viral and cellular genes.

Aim ‒ to evaluate the prophylactic anti-influenza effect of siRNAs directed to the cellular genes NXF1, PRPS1 and NAA10 in an in vitro model.

Materials and methods. Antigenic variants of influenza A virus: A/California/7/09 (H1N1), A/WSN/33 (H1N1) and A/Brisbane/59/07 (H1N1); cell cultures A549 and MDCK. The study was performed using molecular genetic (transfection, NC isolation, RT-PCR-RV) and virological (cell culture infection, titration by visual CPE, viral titer assessment using the Ramakrishnan method) methods.

Results. It was shown that siRNAs targeting the cellular genes NXF1, PRPS1 and NAA10, when used prophylactically in cell culture at a concentration of 0.25 μg per well, during infection with influenza virus strains A/California/7/09 (H1N1), A/WSN/33 (H1N1) and A/Brisbane/59/07 (H1N1) at a multiplicity of infection of 0.01, reduced viral replication to a level of 220 TCID50 per 1 ml of cell medium, whereas in control untreated cells the viral yield was ~106 TCID50 per 1 ml of medium.

Conclusions. Reproduction of influenza A viruses directly depends on the protein products of the NXF1, PRPS1, and NAA10 genes. Reduced expression of these genes disrupts the life cycle and activity of influenza viruses. Such an approach can potentially be studied and used for closely and distantly related representatives of other virus families.

Введение. Грипп – острое респираторное вирусное инфекционное заболевание, индуцируемое одноименными вирусами. Существующие на сегодняшний день профилактические и терапевтические подходы имеют важное противоэпидемическое значение, однако имеется ряд проблем, таких как быстрое возникновение резистентных штаммов, отсутствие формирования перекрестного иммунитета и эффективность вакцин. Одним из подходов в создании противогриппозных средств является использование механизма РНК-интерференции и малых интерферирующих РНК (миРНК), комплементарных к матричной РНК мишени вирусных и клеточных генов.

Цель – оценка профилактического противогриппозного эффекта миРНК, направленных к клеточным генам NXF1, PRPS1 и NAA10, на модели in vitro.

Материалы и методы. Исследовали антигенные варианты вируса гриппа типа А: A/California/7/09 (H1N1), А/WSN/33 (H1N1) и A/Brisbane/59/07 (H1N1); клеточные культуры A549 и MDCK. Исследование выполняли посредством молекулярно-генетических (трансфекции, выделение нуклеиновых кислот, полимеразная цепная реакция с обратной транскрипцией в реальном времени) и вирусологических методов (заражение клеточных культур, титрование по визуальному цитопатическому действию, оценка вирусного титра посредством метода Рамакришнана).

Результаты. Показано, что миРНК, таргетированные к клеточным генам NXF1, PRPS1 и NAA10 при профилактическом применении в клеточной культуре в концентрации 0,25 мкг на лунку, при инфицировании штаммами вируса гриппа A/California/7/09 (H1N1), А/WSN/33 (H1N1) и A/Brisbane/59/07 (H1N1) при множественности инфекции 0,01, снижают вирусную репликацию до уровня 220 ТЦД50 на 1 мл клеточной среды, тогда как в контрольных необработанных клетках вирусный урожай составил ~106 ТЦД50 на 1 мл среды.

Выводы. Снижение экспрессии указанных генов NXF1, PRPS1 и NAA10 приводит к нарушению жизненного цикла и активности вирусов гриппа. Подобный подход может быть потенциально исследован и использован для близко- и дальнородственных представителей иных семейств вирусов.

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