A Novel Mechanism for Zika Virus Host-Cell Binding
by
Courtney A. Rieder 1, Jonathan Rieder 1, Sebastién Sannajust 1,2, Diana Goode 1,2, Ramaz Geguchadze 1,2
, Ryan F. Relich 3, Derek C. Molliver 1,2, Tamara E. King 1,2, James Vaughn 1 and Meghan May 1,2,*
Courtney A. Rieder 1, Jonathan Rieder 1, Sebastién Sannajust 1,2, Diana Goode 1,2, Ramaz Geguchadze 1,2, Ryan F. Relich 3, Derek C. Molliver 1,2, Tamara E. King 1,2, James Vaughn 1 and Meghan May 1,2,*
1
Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA
2
Center for Excellence in the Neurosciences, University of New England, Biddeford, ME 04005, USA
3
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(12), 1101; https://doi.org/10.3390/v11121101
Received: 1 November 2019 / Revised: 19 November 2019 / Accepted: 22 November 2019 / Published: 28 November 2019
(This article belongs to the Special Issue Pathogenesis of Emerging Viral Infections)
Zika virus (ZIKV) recently emerged in the Western 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 emergent Western 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.
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Keywords:
Zika Virus; Neurotropism; Flavivirus; Microcephaly; ASN154; N-acetylglucosamine; Encephalitis; binding motif
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MDPI and ACS Style
Rieder, C.A.; Rieder, J.; Sannajust, S.; Goode, D.; Geguchadze, R.; Relich, R.F.; Molliver, D.C.; King, T.E.; Vaughn, J.; May, M. A Novel Mechanism for Zika Virus Host-Cell Binding. Viruses 2019, 11, 1101.
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