Problems of VirologyProblems of VirologyВопросы вирусологии0507-40882411-2097Central Research Institute for Epidemiology1685910.36233/0507-4088-371nriysaREVIEWSОБЗОРЫReview ArticleDownregulation of SLC7A11 (xCT) expression by influenza A virus (Orthomyxoviridae: Alphainfluenzavirus) as a mechanism for ferroptosis inductionСнижение экспрессии SLC7A11 (xCT) вирусом гриппа A (Orthomyxoviridae: Alphainfluenzavirus) как механизм индукции ферроптозаhttps://orcid.org/0009-0001-5683-873XKorepanovaDaria E.КорепановаДарья Евгеньевна
Russian Federation

Junior Researcher at the Laboratory of Respiratory Viral Infections

младший научный сотрудник лаборатории респираторно-вирусных инфекций

korepanova_de@niivirom.ruhttps://orcid.org/0000-0001-6137-5437ChernyshevaAnna E.ЧернышеваАнна Евгеньевна
Russian Federation

Junior Researcher at the Laboratory of Respiratory Viral Infections

младший научный сотрудник лаборатории респираторно-вирусных инфекций

chernysheva_ae@niivirom.ruFederal Scientific Research Institute of Viral Infections "Virome" Federal Service for Surveillance on Costumer Rights Protection and Human WellbeingФБУН «Федеральный научно-исследовательский институт вирусных инфекций «Виром» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека (Роспотребнадзор)Ural Federal University named after the First President of Russia B.N. YeltsinФГАОУ ВО «Уральский федеральный университет имени первого Президента России Б.Н. Ельцина»3006202671324425324022026Copyright ©; 2026, Korepanova D.E., Chernysheva A.E.Copyright ©; 2026, Корепанова Д.Е., Чернышева А.Е.2026Korepanova D.E., Chernysheva A.E.Корепанова Д.Е., Чернышева А.Е.https://creativecommons.org/licenses/by/4.0https://virusjour.crie.ru/jour/article/view/16859

The aim of the review was to analyze current literature data on the mechanisms by which the influenza A virus causes a decrease in the level of the SLC7A11 (xCT) protein in human cells, which contributes to the initiation of ferroptosis. The literature search was performed in the eLIBRARY.RU, CyberLeninka, Google Scholar, PubMed databases for the period 2009-2026.

Data are presented on the role of the Xc⁻ transport antioxidant system and its key subunit SLC7A11 in the pathogenesis of influenza infection in the context of ferroptosis induction. The Xc− system mediates the import of cystine, which is essential for the synthesis of glutathione, the primary intracellular antioxidant. The molecular mechanisms of ferroptotic cell death are described, including Xc− dysfunction, activation of the transferrin receptor TfR1, lipoxygenase ALOX15. Data on experimental evidence of ferroptosis induction upon influenza virus infection, obtained using A549, 16HBE, BeWo cell lines as well in mouse cells, are presented. This evidence includes increased expression of TRIM family proteins, TNF-α, and elevated TGF-β1 mRNA levels. Hypothetical models of indirect pathogen-mediated effects are discussed, suggesting SLC7A11 suppression driven by pro-inflammatory cytokines (TNF, IFN-γ, IL-1β, TGF-β1) and proteins p53 and BAP1. The need for further research to confirm the contribution of the pathways discussed and to assess their clinical potential as targets for therapy or biomarkers is emphasized.

Цель обзора – анализ современных данных литературы о механизмах, с помощью которых вирус гриппа A вызывает снижение уровня белка SLC7A11 (xCT) в клетках человека, способствуя запуску ферроптоза. Поиск литературы проводили в базах данных eLIBRARY.RU, CyberLeninka, Google Scholar, PubMed за период 2009-2026 гг.

В статье представлены данные о роли транспортной антиоксидантной системы Xc− и ее ключевой субъединицы SLC7A11 в патогенезе гриппозной инфекции в контексте индукции ферроптоза. Система Xc− обеспечивает поступление цистина, необходимого для синтеза глутатиона – главного внутриклеточного антиоксиданта. Дано описание молекулярных механизмов ферроптотической гибели клеток: дисфункция Xc−, активация трансферринового рецептора TfR1, липоксигеназы ALOX15. Представлены сведения об экспериментальных доказательствах индукции ферроптоза при заражении вирусом гриппа, полученные на клеточных линиях A549, 16HBE, BeWo, а также клетках мышей. Среди них – повышение экспрессии белков семейства TRIM, TNF-α, увеличение уровня мРНК TGF-β1. Рассмотрены гипотетические модели опосредованного влияния патогена, предполагающие подавление SLC7A11 провоспалительными цитокинами (TNF, IFN-γ, IL-1β, TGF-β1) и белками p53 и BAP1. Подчеркивается необходимость дальнейших исследований для подтверждения вклада рассмотренных путей и оценки их клинического потенциала в качестве мишеней для терапии или биомаркеров.

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