NKG2C是由具有未表达的缺失变体的基因编码的活化NK细胞受体。巨细胞病毒(CMV)感染扩大了具有适应性样特性的NKG2C+NK细胞群。以前的报告发现,携带删除的NKG2C变体在艾滋病毒感染者(PLWH)中的频率高于未接触艾滋病毒的艾滋病毒对照。在某些研究中,NKG2CNK细胞的频率与HIV病毒载量(VL)呈正相关,而在其他研究中与VL呈负相关。这里,我们在PLWH中调查了NKG2C基因型与HIV易感性和VL设定值之间的联系.对434名PLWH和157名暴露于HIV的血清阴性(HESN)受试者进行了NKG2C基因分型。比较三种可能的NKG2C基因型在这些人群中的分布表明,NKG2C+/+和NKG2C+/-携带者的频率在PLWH和HESN受试者之间没有显着差异,而NKG2C-/-携带者在PLWH中高于HENS受试者,无一例(P=0.03,χ2检验)。我们无法复制至少1个NKG2C-等位基因的携带在PLWH中更频繁。160NKG2C+/+的预处理VL设定点信息可用,83NKG2C+/-,和6NKG2C-/-PLWH。HIVVL设定值在NKG2C基因型之间相似。携带2个NKG2C等位基因的CMVPLWH细胞中,NKG2CCD3-CD14-CD19-CD56dimNK细胞的频率和NK细胞上NKG2C表达的平均荧光强度(MFI)更高。我们观察到VL设定点与NKG2C表达的频率或MFI之间没有相关性。重要性我们比较了尽管多次HIV暴露但仍未感染HIV的受试者(HESN受试者)与PLWH组中的NKG2C等位基因和基因型分布。这使我们能够确定NKG2C基因型是否影响对HIV感染的易感性。HESN受试者中不存在NKG2C-/-基因型,而PLWH则不存在,这表明该基因型的携带与HIV易感性有关。我们计算了252个NKG2C基因分型的PLWH子集中的VL设定点。我们在三种可能的NKG2C基因型的携带者中没有观察到VL设定点的组间差异。NK细胞上NKG2C表达的频率或MFI与巨细胞病毒共感染的PLWH中的VL设定值之间没有发现显着相关性。这些发现表明,适应性NK细胞在建立VL设定点中没有作用,一个参数,是初治HIV疾病进展率的预测指标。
NKG2C is an activating NK cell receptor encoded by a gene having an unexpressed deletion variant. Cytomegalovirus (CMV) infection expands a population of NKG2C+ NK cells with adaptive-like properties. Previous reports found that carriage of the deleted NKG2C- variant was more frequent in people living with HIV (PLWH) than in HIV- controls unexposed to HIV. The frequency of NKG2C+ NK cells positively correlated with HIV viral load (VL) in some studies and negatively correlated with VL in others. Here, we investigated the link between NKG2C genotype and HIV susceptibility and VL set point in PLWH. NKG2C genotyping was performed on 434 PLWH and 157 HIV-exposed seronegative (HESN) subjects. Comparison of the distributions of the three possible NKG2C genotypes in these populations revealed that the frequencies of NKG2C+/+ and NKG2C+/- carriers did not differ significantly between PLWH and HESN subjects, while that of NKG2C-/- carriers was higher in PLWH than in HESN subjects, in which none were found (P = 0.03, χ2 test). We were unable to replicate that carriage of at least 1 NKG2C- allele was more frequent in PLWH. Information on the pretreatment VL set point was available for 160 NKG2C+/+, 83 NKG2C+/-, and 6 NKG2C-/- PLWH. HIV VL set points were similar between NKG2C genotypes. The frequency of NKG2C+ CD3- CD14- CD19- CD56dim NK cells and the mean fluorescence intensity (MFI) of NKG2C expression on NK cells were higher on cells from CMV+ PLWH who carried 2, versus 1, NKG2C+ alleles. We observed no correlations between VL set point and either the frequency or the MFI of NKG2C expression. IMPORTANCE We compared NKG2C allele and genotype distributions in subjects who remained HIV uninfected despite multiple HIV exposures (HESN subjects) with those in the group PLWH. This allowed us to determine whether NKG2C genotype influenced susceptibility to HIV infection. The absence of the NKG2C-/- genotype among HESN subjects but not PLWH suggested that carriage of this genotype was associated with HIV susceptibility. We calculated the VL set point in a subset of 252 NKG2C-genotyped PLWH. We observed no between-group differences in the VL set point in carriers of the three possible NKG2C genotypes. No significant correlations were seen between the frequency or MFI of NKG2C expression on NK cells and VL set point in cytomegalovirus-coinfected PLWH. These findings suggested that adaptive NK cells played no role in establishing the in VL set point, a parameter that is a predictor of the rate of treatment-naive HIV disease progression.