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

by Xie, Ting , Shi, Mang , Zhu, Lin , Zeng, Shike , Zhang, Shengze , Wu, Nan , Luo, Chuming , Wu, Shu , Sun, Caijun , Zou, Xuan , Luo, Huanle , Wu, Jiani , Fang, Shisong , Chen, Qiqi , Zha, Haolu , Tian, Weijian , Li, Nina , Bai, Shaohui , Shu, Yuelong

in Animals / Apoptosis / Biology and Life Sciences / Blood cells / Brain / c-FLIP protein / CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism / Caspase 3 - metabolism / Caspase 8 - metabolism / Caspase-3 / Caspase-8 / Cell death / Dengue fever / Embryos / Encephalitis / Female / Fetuses / FLIP protein / Health aspects / Hepatitis C / Humans / Infections / Inflammation / Inhibitor of apoptosis proteins / Macrophages / Medical research / Medicine and Health Sciences / Medicine, Experimental / Mice / Mice, Inbred C57BL / Mice, Knockout / Microcephaly / Placenta - metabolism / Placenta - pathology / Placenta - virology / Pregnancy / Proteins / Research and Analysis Methods / Uterus / Vector-borne diseases / Viral infections / Virus Replication / West Nile virus / Zika Virus / Zika Virus Infection - metabolism / Zika Virus Infection - pathology / Zika Virus Infection - virology

2024

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

2024

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

2024

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Journal Article

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

Xie, Ting,

Shi, Mang,

Zhu, Lin,

Zeng, Shike,

Zhang, Shengze,

Wu, Nan,

Luo, Chuming,

Wu, Shu,

Sun, Caijun,

Zou, Xuan,

Luo, Huanle,

Wu, Jiani,

Fang, Shisong,

Chen, Qiqi,

Zha, Haolu,

Tian, Weijian,

Li, Nina,

Bai, Shaohui,

Shu, Yuelong

2024

Overview

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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Publisher

Public Library of Science,Public Library of Science (PLoS)

Subject

Animals

/ Apoptosis

/ Biology and Life Sciences

/ Blood cells

/ Brain

/ c-FLIP protein

/ CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism