Influence of KIR gene diversity on the course of HSV-1 infection:: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2
Influence of KIR gene diversity on the course of HSV-1 infection:: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2
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DOI：
10.1111/j.1399-0039.2007.00844.x
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发表时间：
2007-07-01
期刊：
影响因子：
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通讯作者：
Vilches, C.
中科院分区：
文献类型：
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作者：
Estefania, E.;Gomez-Lozano, N.;Vilches, C.
1型单纯疱疹病毒（HSV-1）在大多数人类中引起终身潜伏感染。潜伏在敏感神经节神经元中的周期性病毒再激活导致转运到粘膜皮肤区域并产生复制，从而导致复发性炎性疱疹病变或无症状病毒脱落。这种病变的医学后果和复发的频率在不同的受试者中差别很大。此外，许多受感染的人从未出现该病的症状，即使受到刺激，也会引发其他人的临床复发。1型单纯疱疹病毒感染临床过程中变异的起源仍未得到解释。疱疹病毒和其他病原体破坏受感染细胞的主要组织相容性复合体I类分子的表达，从而破坏t细胞介导的免疫。抗原呈递的颠覆被自然杀伤细胞所抵消，自然杀伤细胞通过特定受体调查人类白细胞抗原（HLA）的表达。其中包括杀手细胞免疫球蛋白样受体（KIRs），它是由一个极其多样化和快速进化的基因复合物编码的。在这里，我们通过比较这些基因在有临床表现的人和无症状感染的供者中的分布，来分析KIR基因多样性对HSV-1感染的可变临床病程的贡献。该研究提供了初步证据，表明受体KIR2DL2和KIR2DS2易导致有症状的HSV-1感染，并有利于频繁复发的疾病形式。HLA-C1配体对HSV-1疾病的可能贡献没有统计学支持。由于KIR2DL2和KIR2DS2之间存在绝对的遗传联系，我们无法确定哪种受体主要负责观察到的关联，但我们的研究结果表明，KIR2DL2和KIR2DS2基因组中的存在阻碍了对HSV-1的有效细胞反应。
Herpes simplex virus type 1 (HSV-1) causes lifelong latent infections in most humans. Periodical virus reactivations from latency in the neurons of sensitive ganglia lead to transport to mucocutaneous regions and productive replication, which results in recurrent inflammatory herpetic lesions or in asymptomatic virus shedding. The medical consequences of such lesions and the frequency of recurrences vary greatly in different subjects. Furthermore, many infected individuals never suffer manifestations of the disease, even when exposed to stimuli that trigger clinical recurrences in other humans. The origin of the variability in the clinical course of HSV-1 infection remains unexplained. Herpesviruses and other pathogens sabotage the expression of major histocompatibility complex class I molecules by infected cells, thus subverting T-cell-mediated immunity. Subversion of antigen presentation is counteracted by natural killer cells, which survey the human leukocyte antigen (HLA) expression by specific receptors. These include the killer cell immunoglobulin-like receptors (KIRs), which are encoded by a complex of extremely diverse and rapidly evolving genes. Here, we analyze the contribution of KIR gene diversity to the variable clinical course of HSV-1 infection by comparing the distribution of these genes in humans with clinical manifestations of the disease with that in asymptomatically infected donors. This study provides preliminary evidence that the receptors KIR2DL2 and KIR2DS2 predispose to symptomatic HSV-1 infection and favor the frequently recurring forms of the disease. Possible contribution of the 'HLA-C1' ligand to HSV-1 disease was not statistically supported. Because of an absolute genetic linkage between KIR2DL2 and KIR2DS2, we could not determine which receptor was primarily responsible for the observed association, but our results suggest that presence in the genome of KIR2DL2 and KIR2DS2 hinders an effective cellular response to HSV-1.