LAMR1 restricts Zika virus infection by attenuating the envelope protein ubiquitination

Virulence. 2021 Dec;12(1):1795-1807. doi: 10.1080/21505594.2021.1948261.

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.

Keywords: E protein; Laminin receptor 1, LAMR1; Zika virus, ZIKV; eukaryotic translation initiation factor 3 subunit 5, EIF3S5; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't