AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa.
PLoS One. 2011 Feb 8;6(2):e16541. doi: 10.1371/journal.pone.0016541.
Numerous studies have suggested a role for natural killer (NK) cells in attenuation of HIV-1 disease progression via recognition by killer-cell immunoglobulin-like receptors (KIRs) of specific HLA class I molecules. The role of KIR and HLA class I has not been addressed in the context of maternal-infant HIV-1 transmission. KIR and HLA class I B and C genes from 224 HIV-1-infected mothers and 222 infants (72 infected and 150 uninfected) from South Africa were characterized. Although a number of significant associations were determined in both the total group and in the nevirapine (NVP) exposed group, the most significant findings involved KIR2DL2 and KIR2DL3 and HLA-C. KIR2DL2/KIR2DL3 was underrepresented in intrapartum (IP)-transmitting mothers compared to non-transmitting (NT) mothers (P = 0.008) and remained significant (P = 0.036) after correction for maternal viral load (MVL). Homozygosity for KIR2DL3 alone and in combination with HLA-C allotype heterozygosity (C1C2) was elevated in IP-transmitting mothers compared to NT mothers (P = 0.034 and P = 0.01 respectively), and after MVL correction (P = 0.033 and P = 0.027, respectively). In infants, KIR2DL3 in combination with its HLA-C1 ligand (C1) as well as homozygosity for KIR2DL3 with C1C2, were both found to be underrepresented in infected infants compared to exposed uninfected infants in the total group (P = 0.06 and P = 0.038, respectively) and in the sub-group of infants whose mothers received NVP (P = 0.007 and P = 0.03, respectively). These associations were stronger post MVL adjustment (total group: P = 0.02 and P = 0.009, respectively; NVP group: P = 0.004 and P = 0.02, respectively). Upon stratification according to low and high MVL, all significant associations fell within the low MVL group, suggesting that with low viral load, the effects of genotype can be more easily detected. In conclusion this study has identified a number of significant associations that suggest an important role for NK cells in maternal-to-infant HIV-1 transmission.
许多研究表明，自然杀伤 (NK) 细胞通过杀伤细胞免疫球蛋白样受体 (KIR) 识别特定的 HLA Ⅰ类分子，在减缓 HIV-1 疾病进展方面发挥作用。在母婴 HIV-1 传播的背景下，尚未研究 KIR 和 HLA Ⅰ类的作用。对来自南非的 224 名 HIV-1 感染母亲和 222 名婴儿（72 名感染和 150 名未感染）的 KIR 和 HLA Ⅰ类 B 和 C 基因进行了特征分析。尽管在总人群和奈韦拉平（NVP）暴露组中确定了许多有意义的关联，但最显著的发现涉及 KIR2DL2 和 KIR2DL3 和 HLA-C。与非传播（NT）母亲相比，分娩时传播（IP）的母亲中 KIR2DL2/KIR2DL3 的表达不足（P=0.008），并且在对母体病毒载量（MVL）进行校正后仍然显著（P=0.036）。与 NT 母亲相比，IP 传播的母亲中 KIR2DL3 单独和与 HLA-C 同种异型杂合性（C1C2）的 KIR2DL3 纯合性升高（P=0.034 和 P=0.01），并且在 MVL 校正后（P=0.033 和 P=0.027，分别）。在婴儿中，与暴露于未感染的婴儿相比，在总组（P=0.06 和 P=0.038，分别）和接受 NVP 的婴儿的亚组中，KIR2DL3 与 HLA-C1 配体（C1）的组合以及 KIR2DL3 与 C1C2 的纯合性均发现与感染的婴儿中 KIR2DL3 表达不足（P=0.007 和 P=0.03，分别）。这些关联在 MVL 调整后更强（总组：P=0.02 和 P=0.009，分别；NVP 组：P=0.004 和 P=0.02，分别）。根据低和高 MVL 进行分层后，所有有意义的关联都在低 MVL 组内，这表明在低病毒载量下，基因型的影响更容易被检测到。总之，这项研究确定了一些有意义的关联，表明 NK 细胞在母婴 HIV-1 传播中发挥重要作用。
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