Prevalence of dengue virus, their infection, diagnosis, and challenges

Abstract

The dengue disease ranges from undifferentiated fever to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The DHF and DSS are the major complications of severe dengue manifestation. The dengue disease is caused by four very similar but serologically distinct dengue virus serotypes (DENV1~4). Although the precise mechanism by which DHF and DSS develop remains undefined, three principal theories, the antibody-dependent enhancement theory, the virulent virus theory, and the T-lymphocyte activation theory, have been recognized predominantly as the major contributors to dengue severity and fatality. Moreover, very little is known on the high frequency of recurrent DENV infections, resurgence of previous serotype with a new one, and presence of concurrent multiple DENV infections in dengue-endemic countries. Furthermore, despite having very similar sequences and structures, all four DENV serotypes might be intrinsically very much different resulting differential immunogenicity (very low to high), and mysterious sero-cross-reacting anti-DENV antibodies restricting the human efforts understanding the dengue disease etiology precisely. The DENV is a single-stranded positive-sense RNA virus that encodes three structural and seven non-structural proteins. Among the 10 proteins the envelope protein constitutes the outermost surface structure of DENVs and is composed of three domains, domain 1 (ED1), domain 2 (ED2), and domain 3 (ED3). The ED3 has been reported to be the major immunogenic domain conferring DENV serospecificity and is involved in host-virus interaction, and antibodies against ED3 could block DENVs under in vitro and in vivo conditions. Therefore, the ED3s of DENV1-4 may be of interest for better understanding of dengue and would be a promising dengue vaccine candidate against all DENV serotypes.