Abstract
This study aims to characterize the antigenicity of the Capsid (C) protein and the human antibody responses to C protein from the four dengue virus (DENV) serotypes. Parker hydrophilicity prediction, Emini surface accessibility prediction and Karplus & Schulz flexibility predictions were used to bioinformatically characterize antigenicity. The human antibody response to C protein was assessed by ELISA using immune sera and an array of overlapping DENV2 C peptides. DENV2 C protein peptides P1 (located on C protein at 2–18 a.a), P11 (79–95 a.a) and P12 (86–101 a.a) were recognized by most individuals exposed to infections with only one of the 4 DENV serotypes as well as people exposed to infections with two serotypes. These conserved peptide epitopes are located on the amino (1–40 a.a) and carboxy (70–100 a.a) terminal regions of C protein, which were predicted to be antigenic using different bioinformatic tools. DENV2 C peptide P6 (39–56 a.a) was recognized by all individuals exposed to DENV2 infections, some individuals exposed to DENV4 infections and none of the individuals exposed to DENV1 or 3 infections. Thus, unlike C peptides P1, P11 and P12, which contain epitopes, recognized by DENV serotype cross-reactive antibodies, DENV2 peptide P6 contains an epitope that is preferentially recognized by antibodies in people exposed to this serotype compared to other serotypes. We discuss our results in the context of the known structure of C protein and recent work on the human B-cell response to DENV infection.
Highlights
Dengue viruses (DENV), arthropod-borne viruses, cause a significant global health burden
The highest level of percentage intra-serotype conservancy of 94.7% was observed for DENV3, which indicates a higher level of genetic similarity among the isolates of DENV3 serotype used for the study
Our results show strong agreement between C peptides predicted by different bioinformatic approaches to be antigenic and peptides recognized by antibodies in people infected with DENV
Summary
Dengue viruses (DENV), arthropod-borne viruses, cause a significant global health burden. The number of cases increases annually, there is only one partially efficacious vaccine registered for prevention [2], and many basic aspects of the viral biology remain elusive.
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