A novel mechanism for zika virus host-cell binding

Abstract

Zika virus (ZIKV) recently emerged in theWestern Hemisphere with previously unrecognized or unreported clinical presentations. Here, we identify two putative binding mechanisms of ancestral and emergent ZIKV strains featuring the envelope (E) protein residue asparagine 154 (ASN154) and viral phosphatidylserine (PS). Synthetic peptides representing the region containing ASN154 from strains PRVABC59 (Puerto Rico 2015) and MR-766 (Uganda 1947) were exposed to neuronal cells and fibroblasts to model ZIKV E protein/cell interactions and bound MDCK or Vero cells and primary neurons significantly. Peptides significantly inhibited Vero cell infectivity by ZIKV strains MR-766 and PRVABC59, indicating that this region represents a putative binding mechanism of ancestral African ZIKV strains and emergentWestern Hemisphere strains. Pretreatment of ZIKV strains MR-766 and PRVABC59 with the PS-binding protein annexin V significantly inhibited replication of PRVABC59 but not MR-766, suggesting that Western hemisphere strains may additionally be capable of utilizing PS-mediated entry to infect host cells. These data indicate that the region surrounding E protein ASN154 is capable of binding fibroblasts and primary neuronal cells and that PS-mediated entry may be a secondary mechanism for infectivity utilized by Western Hemisphere strains.