ABSTRACT

Zika virus (ZIKV) infection can cause severe neurological disorders, including Guillain–Barre syndrome and meningoencephalitis in adults and microcephaly in fetuses. Here, we reveal that laminin receptor 1 (LAMR1) is a novel host resistance factor against ZIKV infection. Mechanistically, we found that LAMR1 binds to ZIKV envelope (E) protein via its intracellular region and attenuates E protein ubiquitination through recruiting the deubiquitinase eukaryotic translation initiation factor 3 subunit 5 (EIF3S5). We further found that the conserved G282 residue of E protein is essential for its interaction with LAMR1. Moreover, a G282A substitution abolished the binding of E protein to LAMR1 and inhibited LAMR1-mediated E protein deubiquitination. Together, our results indicated that LAMR1 represses ZIKV infection through binding to E protein and attenuating its ubiquitination.

摘要

寨卡病毒 (ZIKV) 感染可导致严重的神经系统疾病，包括成人的格林-巴利综合征和脑膜脑炎以及胎儿的小头畸形。在这里，我们揭示了层粘连蛋白受体 1 (LAMR1) 是一种针对 ZIKV 感染的新型宿主抗性因子。从机制上讲，我们发现 LAMR1 与 ZIKV 包膜 (E) 蛋白通过它的细胞内区域并通过招募去泛素酶真核翻译起始因子 3 亚基 5 (EIF3S5) 减弱 E 蛋白泛素化。我们进一步发现E蛋白的保守G282残基对于其与LAMR1的相互作用是必不可少的。此外，G282A 取代消除了 E 蛋白与 LAMR1 的结合，并抑制了 LAMR1 介导的 E 蛋白去泛素化。总之，我们的结果表明 LAMR1 通过与 E 蛋白结合并减弱其泛素化来抑制 ZIKV 感染。