Decreased NK cell frequency and function is associated with increased risk of KIR3DL allele polymorphism in simian immunodeficiency virus-infected rhesus macaques with high viral loads.
Decreased NK cell frequency and function is associated with increased risk of KIR3DL allele polymorphism in simian immunodeficiency virus-infected rhesus macaques with high viral loads.
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DOI：
10.4049/jimmunol.0803580
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发表时间：
2009-03-15
期刊：
影响因子：
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通讯作者：
Ansari AA
中科院分区：
文献类型：
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作者：
Bostik P;Kobkitjaroen J;Tang W;Villinger F;Pereira LE;Little DM;Stephenson ST;Bouzyk M;Ansari AA
NK 细胞已被确定为多种病毒感染中先天免疫的重要效应器。据报道，在人类 HIV-1 感染中，NK 细胞功能、频率和各种 NK 受体表达的改变与疾病进展的差异动力学相关。 NK 细胞上 KIR3DL 和 KIR3DS 受体的某些等位基因的表达与病毒复制水平相关。在感染 SIV 的恒河猴 (RM) 艾滋病模型中，已对与其人类对应物相对应的几个杀伤性抑制性 Ig 相关受体 (KIR 受体) 家族进行了表征，但仅限于单个序列变异的水平。在这里，我们通过分析来自个体动物的多个序列，定义了在 38 个 SIV 感染 RM 中表达的 14 个不同的 KIR3DL 等位基因，其特征是高水平或低水平的 SIV 复制，并显示了这些群体中某些等位基因的不均匀分布。除了这些动物中 NK 细胞的频率和功能下降之外，高水平的 SIV 复制还与 KIR3DL mRNA 水平的显着增加相关。以单核苷酸多态性 159 H/Q 为特征的两个 KIR3DL 等位基因的较高遗传频率与表现出高血浆病毒载量的 RM 相关。该数据首次定义了 RM 中 KIR3DL 的多个等位基因，并显示了病毒控制、NK 细胞功能和 KIR 受体遗传多态性之间的关联。
NK cells have been established as an important effector of innate immunity in a variety of viral infections. In HIV-1 infection in humans, alterations of NK cell function, frequency, and expression of various NK receptors have been reported to be associated with differential dynamics of disease progression. Expression of certain alleles of KIR3DL and KIR3DS receptors on NK cells was shown to correlate with levels of virus replication. In the SIV-infected rhesus macaque (RM) model of AIDS, several families of killer inhibitory Ig-related receptors (KIR receptors) corresponding to their human counterparts have been characterized, but only at the level of individual sequence variants. Here we define 14 different alleles of KIR3DL expressed among 38 SIV-infected RM, characterized by either high or low levels of SIV replication, by analyzing multiple sequences from individual animals and show an unequal distribution of certain alleles in these cohorts. High levels of SIV replication were associated with significant increases in KIR3DL mRNA levels in addition to decreases in both the frequency and function of NK cells in these animals. The higher frequency of inheritance of two KIR3DL alleles characterized by a single nucleotide polymorphism 159 H/Q was associated with RM that exhibited high plasma viral load. This data for the first time defines multiple alleles of KIR3DL in RM and shows an association between virus control, NK cell function and genetic polymorphisms of KIR receptors.