Differential critical residues on the overlapped region of the non-structural protein-1 recognized by flavivirus and dengue virus cross-reactive monoclonal antibodies

Differential critical residues on the overlapped region of the non-structural protein-1 recognized by flavivirus and dengue virus cross-reactive monoclonal antibodies

Blog Article

Abstract The non-structural protein-1 (NS1) of dengue virus (DENV) contributes to several functions related to dengue disease pathogenesis as well as diagnostic applications.Antibodies against DENV NS1 can cross-react with other co-circulating flaviviruses, which may lead to incorrect diagnosis.Herein, five anti-DENV NS1 monoclonal antibodies (mAbs) were investigated.Four of them (1F11, 2E3, 1B2, and 4D2) cross-react with NS1 of all four DENV serotypes (pan-DENV mAbs), whereas the other (2E11) also reacts with NS1 of other flaviviruses (flavi-cross-reactive mAb).

The binding epitopes recognized by these mAbs were found to overlap citronella horse shampoo a region located on the disordered loop of the NS1 wing domain (amino acid residues here 104 to 123).Fine epitope mapping employing phage display technology and alanine-substituted DENV2 NS1 mutants indicates the critical binding residues W115, K116, and K120 for the 2E11 mAb, which are conserved among flaviviruses.In contrast, the critical binding residues of four pan-DENV mAbs include both flavi-conserved residues (W115 to G119) and DENV-conserved flanking residues (K112, Y113, S114 and A121, K122).Our results highlight DENV-conserved residues in cross-reactive epitopes that distinguish pan-DENV antibodies from the flavi-cross-reactive antibody.

These antibodies can be potentially applied to differential diagnosis of DENV from other flavivirus infections.