Bostik Pavel, Kobkitjaroen Jaruda, Tang Weining, Villinger Francois, Pereira Lara E, Little Dawn M, Stephenson Susan T, Bouzyk Mark, Ansari Aftab A
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
J Immunol. 2009 Mar 15;182(6):3638-49. doi: 10.4049/jimmunol.0803580.
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.
自然杀伤细胞（NK细胞）已被确认为多种病毒感染中固有免疫的重要效应细胞。在人类的HIV-1感染中，据报道NK细胞功能、频率以及各种NK受体表达的改变与疾病进展的不同动态相关。NK细胞上KIR3DL和KIR3DS受体某些等位基因的表达与病毒复制水平相关。在艾滋病的猴免疫缺陷病毒（SIV）感染恒河猴（RM）模型中，已鉴定出几个与人类对应物相对应的杀伤抑制性免疫球蛋白相关受体（KIR受体）家族，但仅在个体序列变异水平上。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只感染SIV的RM中表达的14种不同的KIR3DL等位基因，这些RM的特征是SIV复制水平高或低，并显示了这些队列中某些等位基因的分布不均。除了这些动物中NK细胞的频率和功能降低外，SIV的高复制水平还与KIR3DL mRNA水平的显著增加相关。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血浆病毒载量高的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细胞功能与KIR受体基因多态性之间的关联。
