Abstract
The mosquito-borne viral disease caused by the Dengue virus is an expanding global threat. Diagnosis in low-resource-settings and epidemiological surveillance urgently requires new immunoprobes for serological tests. Structure-based epitope prediction is an efficient method to design diagnostic peptidic probes able to reveal specific antibodies elicited in response to infections in patients’ sera. In this study, we focused on the Dengue viral envelope protein (E); computational analyses ranging from extensive Molecular Dynamics (MD) simulations and energy-decomposition-based prediction of potentially immunoreactive regions identified putative epitope sequences. Interestingly, one such epitope showed internal dynamic and energetic properties markedly different from those of other predicted sequences. The epitope was thus synthesized as a linear peptide, modified for chemoselective immobilization on microarrays and used in a serological assay to discriminate Dengue-infected individuals from healthy controls. The synthetic epitope probe showed a diagnostic performance comparable to that of the full antigen in terms of specificity and sensitivity. Given the high level of sequence identity among different flaviviruses, the epitope was immune-reactive towards Zika-infected sera as well. The results are discussed in the context of the quest for new possible structure-dynamics-based rules for the prediction of the immunoreactivity of selected antigenic regions with potential pan-flavivirus immunodiagnostic capacity.
Highlights
Dengue fever is the most important arthropod-borne viral infection in humans; its transmission occurs mostly in urban and semi-urban areas of tropical and sub-tropical climates and has expanded worldwide in recent years [1]
We focused on the Dengue viral envelope protein (E); computational analyses ranging from extensive Molecular Dynamics (MD) simulations and energy-decomposition-based prediction of potentially immunoreactive regions identified putative epitope sequences
Because of its high flexibility the domain is relatively independent from the rest of the protein and is considered to interact with host membrane receptors to start the infection process
Summary
Dengue fever is the most important arthropod-borne viral infection in humans; its transmission occurs mostly in urban and semi-urban areas of tropical and sub-tropical climates and has expanded worldwide in recent years [1]. Serological assays are commonly used for diagnosis of dengue infection as these assays are relatively inexpensive and easy to perform compared with culture or nucleic acid-based methods Even though it is not relevant for diagnosis of the early stages, the detection of dengue-specific immune-response to past infections is of the utmost importance for epidemiological surveillance and to evaluate the risk of severe dengue. This risk is related to the circulation of 4 distinct serotypes of dengue virus: DEN-1, DEN-2, DEN-3 and DEN-4. The World Health Organization (WHO) recommends pre-vaccination screenings to immunize only individuals with evidence of a past dengue infection (seropositive) due to the increased risk of severe dengue in seronegative individuals [3,5]
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