Highly conserved region 141-168 of the NS1 protein is a new common epitope region of Dengue virus

Abstract

Dengue virus (DENV) nonstructural protein 1 (NS1) is a major target of humoral immunity in patients and is believed to be involved in DENV pathogenesis. In addition, NS1 is a diagnostic target as it is secreted, and circulates, in patients' plasma at an early stage of viral infection. In this study, we aimed to identify common epitope regions for all serotypes by preparation of mouse monoclonal antibodies (MAbs) against NS1. A total of 10 out of the 20 hybridoma clones which were specific to DENV produced MAbs that recognized NS1. These MAbs mapped to three regions of DENV-2 NS1, namely amino acids 1-40 (epitope region 1), 141-168 (epitope region 2), and 267-312 (epitope region 3). Epitope region 2 was recognized by both complex-specific (2H11 and 3C4) and subcomplex-specific MAbs (4E5 and 5G12), whereas epitope regions 1 and 3 were recognized by subcomplex-specific MAbs (5E2, 1A5, and 3F10) only. These epitope regions were found to be highly conserved among all four serotypes of DENV by sequence analysis and database comparison. The MAbs against these epitope regions, especially 2H11 and 3C4, could therefore be valuable diagnostic tools.