Mapping Putative B-Cell Zika Virus NS1 Epitopes Provides Molecular Basis for Anti-NS1 Antibody Discrimination between Zika and Dengue Viruses

Abstract

B-cell epitope sequences from Zika virus (ZIKV) NS1 protein have been identified using epitope prediction tools. Mapping these sequences onto the NS1 surface reveals two major conformational epitopes and a single linear one. Despite an overall average sequence identity of ca. 55% between the NS1 from ZIKV and the four dengue virus (DENV) serotypes, epitope sequences were found to be highly conserved. Nevertheless, nonconserved epitope-flanking residues are responsible for a dramatically divergent electrostatic surface potential on the epitope regions of ZIKV and DENV2 serotypes. These findings suggest that strategies for differential diagnostics on the basis of short linear NS1 sequences are likely to fail due to immunological cross-reactions. Overall, results provide the molecular basis of differential discrimination between Zika and DENVs by NS1 monoclonal antibodies.

A Bioinformatic Glimpse of Human-Origin Zika Virus Polyprotein

“…A network analysis can increase insight into the biological organization and the driving forces behind those mutations. However, in the context of infantile microcephaly and the other complications associated with Zika infection, the results reported here, in agreement with the findings of Freire et al [15], suggest that the immunogenicity, toxicity and protective effectiveness of these three peptides should expeditiously be tested experimentally for potential clinical usefulness.…”

“…The data and analysis presented here support and expand the data and analysis presented by Freire et al [15] and therefore suggest that the observed Shannon entropy may be associated with immunological activity. Unfortunately, not all immunological activity is favorable to the infected host.…”

“…Most significant to the bioinformatic parameters reported here, polyprotein amino acid 1118 is a component of a putative 20-mer conformational epitope (CE6) that has been reported [15] for polyprotein amino acids 1105-1124. These 20 amino acids are within the nonstructural protein NS1 domain of the polyprotein; these 20 amino acids occupy numerical positions 311-330 of the mature NS1.…”

“…These 20 amino acids are within the nonstructural protein NS1 domain of the polyprotein; these 20 amino acids occupy numerical positions 311-330 of the mature NS1. This 20-amino acid sequence was computationally identified [15] by structural, conformational and epitopic mapping of Zika virus polyproteins by means of the combined use of Ellipro [16], Epitopia [17] and Discotope [18]. The protein structure and geometric properties are used by Ellipro to computationally predict immunogenic regions of the protein [16].…”

Novel differential linear B‐cell epitopes to identify Zika and dengue virus infections in patients

“…34 Nonetheless, it is imperative to consider the possible implications of virusinfection enhancement. 31,39,40 While various reports have shown the specificity of the NS1 antigen to differentiate between ZIKV and DENV, 11,20,21,41,42 the majority of the common flavivirus peptides identified in this study are on the NS1 protein, possibly because of the conserved regions of NS1 among the flaviviruses. 35,36 Peptides identified from B-cell epitope mapping have been reported on flavivirus E, prM, NS1 and NS3 antigens from antibodies of patients and animal models.…”