Role of N-glycosylation on Zika virus E protein secretion, viral assembly and infectivity

Biochem Biophys Res Commun. 2017 Oct 28;492(4):579-586. doi: 10.1016/j.bbrc.2017.01.022. Epub 2017 Jan 7.

Abstract

Zika virus has rapidly spread reaching a global distribution pattern similar to that of dengue virus, and has been associated with serious neurological and developmental pathologies, like congenital malformation during pregnancy and Guillain-Barré syndrome. Sequence analysis of different clinical and laboratory isolates has shown the existence of mutants with loss of the conserved N-glycosylation motif on domain I of protein E that is common to all flaviviruses. We found that loss of E N-linked glycosylation leads to compromised expression and secretion of E ectodomain from mammalian cells. For both, wild type and glycosylation-negative mutant, secretion was independent of co-expression of the PrM viral protein, but highly dependent on temperature. Low temperature (28 °C) favoured secretion, although the glycosylation mutant E ectodomain showed impaired secretion and membrane display compared to the wild type. Production of pseudoviral particles with a West Nile virus replicon packaged with the Zika virus structural proteins C-PrM-E was significantly reduced with the non-glycosylated E. Similarly, glycosylation-negative pseudoviral particles showed impaired infectivity of Vero cells and reduced ability to infect K562 cells upon particles opsonisation with anti-E antibodies.

Keywords: Envelope protein; Flavivirus; Glycosylation; Infectivity; Secretion; Zika virus.

MeSH terms

  • Animals
  • Glycosylation
  • Humans
  • K562 Cells
  • Protein Domains
  • Vero Cells
  • Viral Envelope Proteins / metabolism*
  • Virus Activation / physiology*
  • Virus Assembly / physiology*
  • Zika Virus / pathogenicity
  • Zika Virus / physiology*
  • Zika Virus Infection / virology*

Substances

  • Viral Envelope Proteins