Abstract

This manuscript is an up-to-date review of experimentally validated linear and continuous epitopes identified from arbovirus members of the Flavivirus genus. We summarized 153 immunoreactive peptides from the Dengue virus, Zika virus, Japanese encephalitis virus, West Nile virus, and tick-borne encephalitis virus described in studies published from 1989 to 2020. We included peptides from structural (envelope, capsid, and pre-membrane) and nonstructural (Ns1–5) viral proteins that demonstrated relevant immunoreactivity with antibodies from naturally infected or vaccinated humans. We included peptides that demonstrated relevant reactivity features, such as indicators of disease severity related to immunological or immunopathological outcomes, differential or group diagnostic markers, immunotherapy candidates, and potential for vaccine formulation. The majority of immunoreactive peptides were described for DENV probably due to its long-lasting impact on human health and the lack of efficient vaccines and therapeutic methods. Immune landscape data regarding linear immunoreactive and continuous flavivirus peptides are still scarce, and a complete and more detailed map remains to be elucidated. Therefore, this review provides valuable data for those investigating the antibody response against flavivirus infection.

Highlights

  • The Flavivirus genus belongs to Flaviviridae family and currently comprises 53 recognized viral species, many of which are important human pathogens (Simmonds et al, 2017)

  • Two linear epitopes from DENV1 (Pep14, AEPDDVDCWCNATDTWV; and Pep15, QRVETWALR HPGFTVIAL) and one from Zika virus (ZIKV) (Pep23, HMCDAT MSYECPMLDEGV) were reported to develop higher detection signal levels with IgG from convalescent ZIKV patients than that from Dengue virus (DENV) patients (Kam et al, 2019). These results suggest that region 43–59 of the DENV1 and ZIKV prM proteins may act as a flavivirus-specific recognition peptide, given that Pep13 and Pep23 respectively were able to recognize the homologous IgG antibodies from convalescent DENV and ZIKV patients with higher detection signal levels

  • The study identified a potential ZIKV-specific peptide (Pep22, SFPTTLGMNKCYIQIMDL) and a DENV3 cross-reactive peptide (Pep19, LFKTASGINMCTLIAMDL) on the prM region. These peptides reacted at higher rates with IgG from convalescent ZIKV patients compared with that from convalescent DENV patients. These results suggest that the DENV3 and ZIKV prM proteins both contain potential virusspecific linear peptides as well as potential cross-reactive linear peptides, which may provide relevant diagnostic tools and develop important roles during flavivirus infection

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Summary

Introduction

The Flavivirus genus belongs to Flaviviridae family and currently comprises 53 recognized viral species, many of which are important human pathogens (Simmonds et al, 2017). These results suggest that region 43–59 of the DENV1 and ZIKV prM proteins may act as a flavivirus-specific recognition peptide, given that Pep13 and Pep23 respectively were able to recognize the homologous IgG antibodies from convalescent DENV and ZIKV patients with higher detection signal levels.

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