Abstract
The dengue virus (DENV) envelope protein domain III (ED3) has been suggested to contain receptor recognition sites and the critical neutralizing epitopes. Up to date, relatively little work has been done on fine mapping of neutralizing epitopes on ED3 for DENV4. In this study, a novel mouse type-specific neutralizing antibody 1G6 against DENV4 was obtained with both prophylactic and therapeutic effects. The epitope was mapped to residues 387–390 of DENV4 envelope protein. Furthermore, site-directed mutagenesis assay identified two critical residues (T388 and H390). The epitope is variable among different DENV serotypes but is highly conserved among four DENV4 genotypes. Affinity measurement showed that naturally occurring variations in ED3 outside the epitope region did not alter the binding of mAb 1G6. These findings expand our understanding of the interactions between neutralizing antibodies and the DENV4 and may be valuable for rational design of DENV vaccines and antiviral drugs.
Highlights
Dengue is the most important arbovirus disease in tropical and subtropical countries
A total of 14 mAbs against different Dengue viruses (DENV) serotypes were obtained by both enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA) (S1 Fig and S1 Table)
Indirect ELISA and Western blot based on DENV1-4 rED3s further confirmed that mAb 1G6 only reacted with DENV4 ED3 protein (Fig 1B and 1C)
Summary
Dengue is the most important arbovirus disease in tropical and subtropical countries. Clinical symptoms range from a self-limited, acute, febrile disease called dengue fever (DF) to severe dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS)[1]. It was estimated that over 2.5 billion people are at risk of contracting dengue, and that about 390 million people are infected with dengue every year, resulting in 100 million symptomatic infections with 250,000 cases of DHF/DSS per year worldwide [2,3,4]. Dengue viruses (DENV) are composed of four genetically and antigenically related viruses termed DENV1-4 [5]. They have a relatively simple enveloped virion that is 50 nm in diameter and consist of a capsid protein (C), membrane protein (M), and a major envelope glycoprotein (E). The E protein ectodomain can be divided into three structural domains designated domain
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