Abstract

Dengue is currently one of the most important arbovirus infections worldwide. Early diagnosis is important for disease outcome, particularly for those afflicted with the severe forms of infection. The goal of this work was to identify conserved and polymorphic linear B-cell Dengue virus (DENV) epitopes that could be used for diagnostic purposes. To this end, we aligned the predicted viral proteome of the four DENV serotype and performed in silico B-cell epitope mapping. We developed a script in Perl integrating alignment and prediction information to identify potential serotype-specific epitopes. We excluded epitopes that were similarly present in the yellow fever and zika viruses’ proteomes. A total of 15 polymorphic and nine conserved peptides among DENV serotypes were selected. Peptides were spotted on cellulose membranes and tested against sera from rabbits that were monoinfected with each DENV serotype. Although serotype-specific peptides failed to recognize any sera, three conserved peptides were recognized by all anti-dengue sera and were included on an ELISA test employing a well-characterized human sera bank. Of the three peptides, one was able to efficiently identify sera from all four DENV serotypes and to discriminate them from Zika virus positive sera.

Highlights

  • Dengue is currently considered as one of the most important arbovirus’ infections in the world.Almost half of the world’s population-or 3.9 billion people in 128 countries-live in areas where there is a considerable risk of Dengue virus (DENV) transmission [1,2]

  • Prediction of conserved B-cell linear epitopes amongst the four DENV serotypes with specificity set to 96% or greater resulted in 9 selected sequences of 8 or more amino acids

  • The differential serological diagnosis amongst the four serotypes of DENV, Zika virus (ZIKV) and other arboviruses is difficult due to the existence of cross reactions between antibodies generated against one of viruses and other related pathogens, especially those caused by viruses on the same viral family, as it is the case of the flaviviruses

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Summary

Introduction

Dengue is currently considered as one of the most important arbovirus’ infections in the world. Almost half of the world’s population-or 3.9 billion people in 128 countries-live in areas where there is a considerable risk of Dengue virus (DENV) transmission [1,2]. Estimates show that 390 million people are infected annually, of which about 96 million result in infections ranging from minimally symptomatic to severe [3]. Dengue viruses are transmitted through the bite of the female mosquito of the species Aedes aegypti or other species within the Aedes genus [4]. The viruses belong to the Flaviviridae family-Flavivirus genus-and there are four DENV serotypes (DENV-1, DENV-2, DENV-3 and DENV-4), which are genetically and antigenically related [5]. An infection with a single serotype leads to long-lasting

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