Genome-Wide Analysis to Identify HLA Factors Potentially Associated With Severe Dengue.
Genome-Wide Analysis to Identify HLA Factors Potentially Associated With Severe Dengue.
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DOI：
10.3389/fimmu.2018.00728
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发表时间：
2018
影响因子：
7.3
通讯作者：
Biswas D
中科院分区：
文献类型：
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作者：
Gupta S;Agarwal A;Kumar A;Biswas D
登革病毒（DENV）感染后，登革出血热（DHF）的发病机制是一个复杂且鲜为人知的现象。鉴于临床上需要识别出更有可能出现这种严重后果的患者，我们对ViPR数据库中已报道的与登革热和登革出血热有差异相关性的序列中的表位变异进行了全基因组比较关联分析。在列举出相关的表位变异后，我们确定了相应的人类白细胞抗原（HLA）等位基因，在这些等位基因的背景下，登革病毒感染可能引发登革出血热。我们的分析从三个不同的角度考虑了登革出血热的发展：（a）作为初次登革病毒感染的结果，（b）在感染了不同血清型的登革病毒的二次感染之后，（c）在感染了相关黄病毒（如寨卡病毒、日本脑炎病毒、西尼罗河病毒等）之后又感染登革病毒的结果。经过实验验证，由于不良预后结果的风险相对较高，这些病毒和宿主标志物在对登革病毒感染患者进行分流以便更密切监测方面将具有重要价值，并且在大规模疫情爆发期间对稀缺的机构资源进行合理分配也很有价值。
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.