ecodagЮг России: экология, развитиеSouth of Russia: ecology, development1992-10982413-0958State Institute of Applied Ecology of the Republic of Dagestan10.18470/1992-1098-2024-4-5ecodag-3299Research ArticleВИРУСОЛОГИЯVIROLOGYПротивовирусная активность модифицированных олигонуклеотидов в лимфоидных клетках человека, инфицированных ВИЧ‐1Antiviral activity of modified oligonucleotides in human lymphoid cells infected with a strain of HIV‐1https://orcid.org/0000-0001-5896-8231ГотфридЛ. Г.GotfridL. G.

Людмила Г. Готфрид, м.н.с.

630559, рп. Кольцово, Новосибирская область. Тел. +79134506795

Ludmila G. Gotfrid, Junior Researcher

ABK 12A, Koltsovo, Novosibirsk Oblast, 630559. Tel. +79134506795

gotfrid_lg@vector.nsc.ruhttps://orcid.org/0000-0001-7889-6319ПавловаА. С.PavlovaA. S.

Анна С. Павлова

Новосибирск

Anna S. Pavlova

Novosibirsk

https://orcid.org/0000-0002-2300-7809КупрюшкинМ. С.KupryushkinM. S.

Максим С. Купрюшкин

Новосибирск

Maxim S. Kupryushkin

Novosibirsk

https://orcid.org/0000-0002-7559-2376ПышнаяИ. А.PyshnayaI. A.

Инна А. Пышная

Новосибирск

Inna A. Pyshnaya

Novosibirsk

https://orcid.org/0000-0002-0891-0880ГашниковаН. М.GashnikovaN. M.

Наталья М. Гашникова

Кольцово

Natalya M. Gashnikova

Koltsovo

ФБУН Центр Роспотребнадзора «Вектор»РоссияVector State Research Centre of Virology and BiotechnologyRussian FederationИнститут химической биологии и фундаментальной медицины СО РАНРоссияInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of SciencesRussian FederationФБУН Центр Роспотребнадзора «Вектор»РоссияVector State Research Centre of Virology and Biotechnology, RospotrebnadzorRussian Federation2024220120251945767Copyright © Готфрид Л.Г., Павлова А.С., Купрюшкин М.С., Пышная И.А., Гашникова Н.М., 20252025Готфрид Л.Г., Павлова А.С., Купрюшкин М.С., Пышная И.А., Гашникова Н.М.Gotfrid L.G., Pavlova A.S., Kupryushkin M.S., Pyshnaya I.A., Gashnikova N.M.This work is licensed under a Creative Commons Attribution 4.0 License.https://ecodag.elpub.ru/ugro/article/view/3299

Цель – исследовать способность к проникновению в клетки и антиретровирусные свойства модифицированных олигодезоксири‐бонуклеотидов, направленных на высоко консервативные участки генома ВИЧ‐1. Исследование проводили с использованием модифицированных олигонуклеотидов, содержащих тиофосфатные, фосфорилгуанидиновые или додецильные остатки.Изучение способности олигонуклеотидов к ингибированию вируса было проведено с использованием модели лимфоидной культуры клеток человека МТ4, инфицированных охарактеризованным высокопродуктивным штаммом ВИЧ‐1, относящимся к геноварианту субтипа А6, широко распространенного на территории Российской Федерации. Оценку проникновения олигонуклеотидов в клетки МТ4 проводили методом конфокальной микроскопии.Показано, что тиофосфат‐ и додецил‐содержащие олигонуклеотиды способны проникать внутрь клеток без использования каких‐либо дополнительных трансфецирующих агентов. Установлено, что тиофосфатные олигонуклеотиды, трансфецированные в составе дуплекса с додецил‐содержащими производными, локализуются внутри клетки в ядре и ядрышке и способны подавлять репродукцию высокопродуктивного штамма ВИЧ‐1. Для исследованных олигонуклеотидных производных определены 50%‐ная токсичная доза (ТС50) и 50%‐ная ингибирующая концентрация (IC50), значение которой в случае тиофосфатных олигонуклеотидов составило менее 0,5 мкМ.Полученные данные свидетельствуют о возможности использования исследованных модифицированных олигонуклеотидов в качестве потенциальных противовирусных агентов в отношении ВИЧ‐1.

Aim. To investigate the cell entry and antiretroviral properties of modified oligodeoxyribonucleotides targeting highly conserved regions of the HIV‐1 genome: the study was conducted using modified oligonucleotides containing phosphorothioate, phosphorylguanidine or dodecyl moieties.The ability of oligonucleotides to inhibit the virus was studied using a model of lymphoid culture of human MT4 cells infected with a characterised high‐productive strain of HIV‐1 belonging to the subtype A6 genovariant widely spread in the Russian Federation. The entry of oligonucleotides into MT4 cells was assessed by confocal microscopy.It was shown that phosphorothioate‐ and dodecyl‐containing oligonucleotides are able to penetrate inside cells without the use of any additional transfection agents. It was found that phosphorothioate oligonucleotides transfected in duplex with dodecyl‐containing derivatives were localized inside the cell in the nucleus and nucleolus and were able to inhibit the reproduction of a highly productive HIV‐1 strain. A 50% toxic dose (TC50) and a 50% inhibitory concentration (IC50) were determined for the oligonucleotide derivatives studied, the value of which was less than 0,5 μM in the case of phosphorothioate oligonucleotides.The data obtained indicate the ability of the modified oligonucleotides studied to be used as potential antiviral agents against HIV‐1.

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The authors declare that there are no conflicts of interest present.