ZIKV infection causes placental inflammation through activating PANoptosis

作者：Shuqing Zhang, Delin Chen, Kexin Zhang, Minjie Liu, H. Liang, Linyue Liang, Jingyao Liang, Minqi Liang, Shu An, Mingcui Lyu, Zhu Junying, Shangwei Li, Dingwen Hu, Xun Zhu, Jueheng Wu, Zhenjian He, Mengfeng Li · 发表于：Journal of Virology · 年份：2025 · DOI：10.1128/jvi.01759-25 · 被引用次数：6 · 研究领域：Mosquito-borne diseases and control、Inflammasome and immune disorders、interferon and immune responses

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. IMPORTANCE Zika 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 reg...