c-FLIP facilitates ZIKV infection by mediating caspase-8/3-dependent apoptosis.
PLoS Pathog
; 20(7): e1012408, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-39038037
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Apoptose
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Caspase 3
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Caspase 8
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Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD
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Zika virus
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Infecção por Zika virus
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article