Regional Virology Laboratory, Department of Microbiology, All India Institute of Medical Sciences Bhopal, Bhopal, India.
Front Immunol. 2018 Apr 10;9:728. doi: 10.3389/fimmu.2018.00728. eCollection 2018.
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.
登革出血热（DHF）的发病机制是一个复杂且尚未完全了解的现象。鉴于临床需要识别出更有可能出现这种严重后果的患者，我们对 ViPR 数据库中已报告与登革热和 DHF 差异相关的序列中的表位变异体进行了全基因组关联分析。在枚举了有嫌疑的表位变异体之后，我们确定了相应的 HLA 等位基因，在这些等位基因中，DENV 感染可能会引发 DHF。我们的分析从三个不同的角度考虑了 DHF 的发展：（a）作为原发性 DENV 感染的结果，（b）继异型 DENV 感染之后，（c）在感染相关的黄病毒（如寨卡病毒、日本脑炎病毒、西尼罗河病毒等）之后感染 DENV。这些病毒和宿主标志物经过实验验证后，将有助于对 DENV 感染患者进行分诊，以便进行更密切的监测，因为这些患者预后较差的风险相对较高，并且在大爆发期间也有助于合理分配稀缺的机构资源。
