Monkeypox virus induces ferroptosis to facilitate viral replication and promotes inflammatory responses

• Published in: Emerging microbes & infections Vol. 14; no. 1; p. 2522877
• Main Authors: Chuai, Xia, Wang, Yuping, Wang, Chen, Ye, Tianxi, Shen, Xiaofan, Zhou, Jinge, Zhang, Kaiyue, Zhao, Baoxin, Wu, Yan, Li, Wujian, Cai, Zhigang, Chiu, Sandra
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 31.12.2025; Taylor & Francis Group
• Subjects: Animals; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Ferroptosis; Host-Pathogen Interactions; Humans; Inflammation - virology; inflammatory responses; Mice; Mice, Inbred C57BL; Monkeypox virus - physiology; Mpox, Monkeypox - immunology; Mpox, Monkeypox - virology; MPXV; PTGS2; Vaccinia virus - physiology; Virus Replication; inflammatory responses; ferroptosis; PTGS2; MPXV; virus replication
• ISSN: 2222-1751; 2222-1751
• DOI: 10.1080/22221751.2025.2522877

Ferroptosis is an iron-dependent form of programmed cell death, which is characterized by iron overload and accumulation of lipid peroxidation. As a newly identified type of cell death, its involvement in poxvirus infection and pathogenesis remains unclear. Since MPXV shares biological and pathogenic similarities with other poxviruses, such as vaccinia virus (VACV), we used VACV-infected cell and mouse models to demonstrate that VACV infection induces ferroptosis both in vitro and in vivo. Inhibition of ferroptosis significantly reduce virus replication and alleviates the inflammatory response. Additionally, we observed that VACV infection upregulates prostaglandin-endoperoxide synthase 2 (PTGS2), which contributes to virus-triggered ferroptosis and inflammation. This study identifies a novel form of cell death triggered by poxvirus infection, shedding light on host-pathogen interactions and offering a potential therapeutic target for MPXV and other .