Lack of association of the KIR and HLA class I ligands with ZIKV infection in south and southeast of Brazil

BACKGROUND Zika virus (ZIKV) is an emerging arbovirus associated with foetal malformations and neurological complications. The infection is usually associated with mild symptoms. The comparison between the allelic frequency of polymorphic genes in symptomatic infected individuals in the population can clarify the pathogenic mechanisms of ZIKV. During ZIKV infection, cytokines are produced and natural killer (NK) cells are recruited, whose activation depends on signaling pathways activated by specific receptors, such as killer cell immunoglobulin-like receptors (KIR). These molecules interact with human leukocyte antigen (HLA) class I ligands and are encoded by polymorphic genes. OBJECTIVES This study aimed to evaluate the frequency of allelic variants of the genes encoding the KIR receptors and their HLA class I ligands in 139 symptomatic ZIKV-patients and 170 controls negative for the virus, and to evaluate the role of these variants for ZIKV susceptibility. METHODS KIR and HLA class I genes were genotyped using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique. FINDINGS No significant differences in the frequency distribution of KIRs and KIR-HLA in patients compared to controls were observed. MAIN CONCLUSIONS KIR and its HLA ligands might play a minor role in ZIKV infection in the south and southeast Brazilian individuals.

背景：寨卡病毒（Zika virus, ZIKV）是一种新兴虫媒病毒，与胎儿畸形及神经系统并发症密切相关。该病毒感染通常仅引发轻症症状。对人群中有症状感染者体内多态性基因的等位基因频率进行比较分析，可阐明寨卡病毒的致病机制。寨卡病毒感染过程中，机体可产生细胞因子并招募自然杀伤（natural killer, NK）细胞；NK细胞的活化依赖于特定受体激活的信号通路，这类受体包括杀伤细胞免疫球蛋白样受体（killer cell immunoglobulin-like receptor, KIR）。此类分子可与人类白细胞抗原（human leukocyte antigen, HLA）I类配体结合，且由多态性基因编码。
研究目的：本研究旨在对139例有症状寨卡病毒感染患者以及170例病毒检测阴性的对照个体中，编码KIR受体及其HLA I类配体的基因等位变异频率进行评估，并分析上述变异在寨卡病毒易感性中的作用。
研究方法：采用聚合酶链反应-序列特异性寡核苷酸（polymerase chain reaction-sequence specific oligonucleotide, PCR-SSO）技术，对KIR及HLA I类基因进行基因分型。
研究结果：与对照组相比，患者组的KIR基因及KIR-HLA组合的频率分布未观察到显著差异。
主要结论：在巴西南部及东南部人群中，KIR及其HLA配体可能在寨卡病毒感染过程中仅发挥次要作用。