2. Academic Validation
  3. c-FLIP facilitates ZIKV infection by mediating caspase-8/3-dependent apoptosis

c-FLIP facilitates ZIKV infection by mediating caspase-8/3-dependent apoptosis

  • PLoS Pathog. 2024 Jul 22;20(7):e1012408. doi: 10.1371/journal.ppat.1012408.
Shengze Zhang 1 2,  Nina Li 1 2 3,  Shu Wu 1 2,  Ting Xie 1 2,  Qiqi Chen 1 2,  Jiani Wu 1 2,  Shike Zeng 1 2,  Lin Zhu 1 2,  Shaohui Bai 1 2,  Haolu Zha 1 2,  Weijian Tian 1 2,  Nan Wu 4,  Xuan Zou 5,  Shisong Fang 5,  Chuming Luo 1 2,  Mang Shi 6,  Caijun Sun 1 2 7,  Yuelong Shu 1 7 8,  Huanle Luo 1 2 7
Affiliations

Affiliations

  • 1 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen Campus of Sun Yat-sen University, Shenzhen, P.R. China.
  • 2 School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, P.R. China.
  • 3 Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
  • 4 Shenzhen Nanshan Center for Disease Control and Prevention, Shenzhen, P.R. China.
  • 5 Shenzhen Center for Disease Control and Prevention, Shenzhen, P.R. China.
  • 6 The Centre for Infection and Immunity Studies, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China.
  • 7 Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, P.R. China.
  • 8 Key Laboratory of Pathogen Infection Prevention and Control (MOE), State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
PMID: 39038037 DOI: 10.1371/journal.ppat.1012408
Abstract

c-FLIP functions as a dual regulator of Apoptosis and inflammation, yet its implications in Zika virus (ZIKV) Infection remain partially understood, especially in the context of ZIKV-induced congenital Zika syndrome (CZS) where both Apoptosis and inflammation play pivotal roles. Our findings demonstrate that c-FLIP promotes ZIKV Infection in placental cells and myeloid-derived macrophages, involving inflammation and Caspase-8/3-mediated Apoptosis. Moreover, our observations reveal that c-FLIP augments ZIKV Infection in multiple tissues, including blood cell, spleen, uterus, testis, and the brain of mice. Notably, the partial deficiency of c-FLIP provides protection to embryos against ZIKV-induced CZS, accompanied by a reduction in caspase-3-mediated Apoptosis. Additionally, we have found a distinctive parental effect of c-FLIP influencing ZIKV replication in fetal heads. In summary, our study reveals the critical role of c-FLIP as a positive regulator in Caspase-8/3-mediated Apoptosis during ZIKV Infection, significantly contributing to the development of CZS.

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