Genome-Wide Analysis to Identify HLA Factors Potentially Associated With Severe Dengue

Abstract

The pathogenesis of dengue hemorrhagic fever (DHF), following dengue virus (DENV) infection, is a complex and poorly understood phenomenon. In view of the clinical need of identifying patients with higher likelihood of developing this severe outcome, we undertook a comparative genome-wide association analysis of epitope variants from sequences available in the ViPR database that have been reported to be differentially related to dengue fever and DHF. Having enumerated the incriminated epitope variants, we determined the corresponding HLA alleles in the context of which DENV infection could potentially precipitate DHF. Our analysis considered the development of DHF in three different perspectives: (a) as a consequence of primary DENV infection, (b) following secondary DENV infection with a heterologous serotype, (c) as a result of DENV infection following infection with related flaviviruses like Zika virus, Japanese Encephalitis virus, West Nile virus, etc. Subject to experimental validation, these viral and host markers would be valuable in triaging DENV-infected patients for closer supervision owing to the relatively higher risk of poor prognostic outcome and also for the judicious allocation of scarce institutional resources during large outbreaks.

Uncovering the Burden of Dengue in Africa: Considerations on Magnitude, Misdiagnosis, and Ancestry

“…Different human leukocyte antigen (HLA) groups have also been shown to confer either protection against or risk of developing severe dengue manifestations, including HLA-A 0203, 0207, A11, B-15, B-44, B-46, B-48, B-51, and B-52, which have different effects in various ethnic groups [204,205]. Some HLA types associated with more severe dengue disease include but are not limited to HLA-A*31, A*01, A*26, A*31, A*68, A*32, and A*30, as well as B*44, B*15, and B*35:01 [206]. Several HLA types associated with protection from severe disease include HLA-DR*9, DR*12, B*07, and DR*13 [207].…”

Dengue: a growing threat requiring vaccine development for disease prevention

“…The exact causes of severe dengue still remain elusive. The etiology of severe dengue is undoubtedly multifactorial with host factors and immune status having important roles [15][16][17]. The question of the existence of biological markers of severe dengue as prognostic signatures of the risk of evolution of disease was addressed [18,19].…”