State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan China.
Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou China.
Virulence. 2021 Dec;12(1):1795-1807. doi: 10.1080/21505594.2021.1948261.
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 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.
寨卡病毒（ZIKV）感染可引起严重的神经疾病，包括成人中的格林-巴利综合征和脑膜脑炎，以及胎儿中的小头畸形。在这里，我们揭示层粘连蛋白受体 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）蛋白的细胞内区域结合，并通过招募去泛素化酶真核翻译起始因子 3 亚基 5（EIF3S5）来减弱 E 蛋白的泛素化。我们进一步发现 E 蛋白的保守 G282 残基对于其与 LAMR1 的相互作用至关重要。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，我们的研究结果表明，LAMR1 通过与 E 蛋白结合并减弱其泛素化来抑制 ZIKV 感染。
