Identification of antiviral RNAi regulators, ILF3/DHX9, recruit at ZIKV stem loop B to protect against ZIKV induced microcephaly.

ABSTRACT: Zika virus (ZIKV) is a member of the Flaviviridae family and causes congenital microcephaly and Guillain-Barré syndrome. Currently, there is a lack of approved vaccines or therapies against ZIKV infection. In this study, we profile vRNA‒host protein interactomes at ZIKV stem‒loop B (SLB) and reveal that interleukin enhancer binding factor 3 (ILF3) and DEAH-box helicase 9 (DHX9) form positive regulators of antiviral RNA inference in undifferentiated human neuroblastoma cells and induced pluripotent stem cell-derived human neural stem cells (iPSC-NSCs). Functionally, ablation of ILF3 in brain organoids and Nestin-Cre ILF3 cKO foetal mice significantly enhance ZIKV replication and aggravated ZIKV-induced microcephalic phenotypes. Mechanistically, ILF3/DHX9 enhance DICER processing of ZIKV vRN

SUBMITTER: Lei Z 

PROVIDER: S-EPMC11865596 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature