ArticleJournal of virology2025
ZIKV infection causes placental inflammation through activating PANoptosis.
Article in Journal of virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- PANoptosis in life and death across cell types: From innate immunity to therapeutic implications.Cell chemical biology · 2026Review
- Study on the effect of Ursolic acid on liver cancer cells using z-vad-fmk and ROS inhibitors.Cytotechnology · 2026Article
- Mouse models of Zika virus infection-induced placenta and fetal brain damage.Journal of animal science · 2026Review
- PANoptosis nexus in ischemia-reperfusion injury: from integrated cell death mechanisms to novel therapeutic opportunities.Frontiers in immunology · 2026Review
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Authors and funding
17 authors.
Funding
Abstract
Infection by the Zika virus (ZIKV) during pregnancy can cause congenital Zika syndrome (CZS) or other central nervous system conditions in infants, underscoring the importance of understanding the role of ZIKV-induced placental damage in the development of CZS. Here, we established a ZIKV-infected pregnant mouse model and examined the pathological changes in the placenta following ZIKV infection. We found that ZIKV infection induces severe placental inflammation associated with trophoblast PANoptosis. Specifically, ZIKV activates RIG-I and recruits ASC, caspase-1, NLRP3, caspase-8, and RIPK1 to form a PANoptosome complex, leading to the activation of PANoptosis. Moreover, the combined use of Z-VAD-FMK with GSK872 or with the RIG-I inhibitor RIG012 robustly suppressed ZIKV-induced cell death, attenuated the inflammatory response in trophoblast cells and the placenta induced by ZIKV infection. Collectively, we elucidate a previously unrecognized mechanism by which ZIKV infection causes severe placental inflammation by activating PANoptosis and provide a foundation for the potential application of anti-PANoptotic therapy against ZIKV-associated diseases.IMPORTANCEZika virus (ZIKV), a mosquito-borne virus, has caused significant disease in humans during outbreaks over the last decade. Currently, there is no approved preventive vaccine or specific therapeutic drug against ZIKV. The World Health Organization declared a Public Health Emergency of International Concern regarding microcephaly and other neurological disorders caused by ZIKV during pregnancy in 2016, highlighting the importance of understanding the role of the maternal-fetal barrier in this viral disease. The mechanism by which ZIKV causes placental pathogenesis, however, remains unclear. In this study, our data elucidate a previously unrecognized mechanism underlying ZIKV infection that causes severe placental inflammation by activating PANoptosis. Furthermore, we propose a treatment that effectively inhibits ZIKV-induced PANoptosis and attenuates the inflammatory response in trophoblast cells
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