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Updated: Jan 2, 2026
Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
Published on: August 23, 2016
A Novel Mechanism for Zika Virus Host-Cell Binding
Courtney A Rieder1, Jonathan Rieder1, Sebastién Sannajust1,2
1Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England; Armidale NSW 2351, Australia.
Abstract:
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.
Insights
Zika virus (ZIKV) binding involves the E protein
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Zika virus (ZIKV) emerged in the Western Hemisphere with novel clinical presentations.
- Understanding ZIKV entry mechanisms is crucial for developing antiviral strategies.
Purpose of the Study:
- To identify putative binding mechanisms of ancestral and emergent ZIKV strains.
- To investigate the role of the E protein residue asparagine 154 (ASN154) and phosphatidylserine (PS) in ZIKV infection.
Main Methods:
- Synthetic peptides representing the ASN154 region of ZIKV strains were used to model E protein/cell interactions.
- Interactions were tested with neuronal cells, fibroblasts, MDCK, and Vero cells.
- Annexin V was used to assess the role of PS-mediated entry.
Main Results:
- Peptides containing ASN154 significantly bound to and inhibited infectivity in various cell types, including neuronal cells.
- This region represents a conserved binding mechanism for both African and Western Hemisphere ZIKV strains.
- Western Hemisphere strains may utilize PS-mediated entry as a secondary infection mechanism.
Conclusions:
- The region surrounding E protein ASN154 is critical for ZIKV binding to host cells, including neurons and fibroblasts.
- Phosphatidylserine-mediated entry appears to be an additional mechanism for Western Hemisphere ZIKV strains.
- These findings provide insights into ZIKV pathogenesis and potential therapeutic targets.
