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

MeSH terms

  • Humans
  • Receptors, Laminin / metabolism*
  • Ribosomal Proteins / metabolism*
  • Ubiquitination*
  • Viral Envelope Proteins / chemistry*
  • Zika Virus
  • Zika Virus Infection*

Substances

  • RPSA protein, human
  • Receptors, Laminin
  • Ribosomal Proteins
  • Viral Envelope Proteins

Grants and funding

This work was supported by the Guangdong Province Introduction of Innovative R&D Team [2017ZT07Y580]; Innovative Research Group Project of the National Natural Science Foundation of China [81730061]; Research Hong Kong Scholar Program [XJ2019052]; National Natural Science Foundation of China [81902053]; Postdoctoral Research Foundation of China [2018T110923].