有些人似乎对艾滋病具有天生的免疫力，他们经常处于艾滋高危环境中，却从不会被感染。加拿大科学家近日研究称，这可能要归功于他们体内同时表达了两种特殊基因——KIR3DL1和HLA-B*57。取决于拥有这两个基因的“版本”的不同，他们或是能抵御HIV感染，或是艾滋发展速度变慢。相关论文发表在《艾滋病》（AIDS）上。
领导此次研究的是加拿大麦吉尔大学健康中心的Nicole Bernard。研究人员比较了遭受艾滋病毒急性感染者和重复暴露于艾滋病毒却未被感染者的遗传资料。群组研究分析表明，这两个基因的“好”版本出现在12.2%重复暴露却未被感染者体内，而在急性感染者中比例只有2.7%。
目前，尚未有研究能清楚地解释这种保护机制。KIR3DL1基因编码免疫系统天然杀手细胞（NK）表面的受体，NK细胞被激活后能摧毁受感染的细胞。HLA-B*57基因编码一个通常能在所有人体细胞表面发现的受体，它绑定KIR3DL1并会抑制NK细胞的活性。
研究人员提出一个最可能的假设认为，HIV阻止了HLA-B*57编码的蛋白在受感染的细胞表面进行表达，使其无法绑定KIR3DL1。结果，NK细胞保持活性并摧毁被病毒感染的细胞。当艾滋病毒开始感染人体细胞时，这一机制能迅速发挥作用，携带特定版本这两个基因的人或许就能够更有效地破坏受感染的细胞，从而降低他们感染艾滋的机会。
Bernard说：“还需要更多的研究以确定精确的机制，不过这些发现已经揭示了一个有希望的路径。”这一研究为抵御HIV感染开辟了新思路，Bernard说：“将来我们的发现可被用于在一定程度上加强先天免疫系统，从而在艾滋病毒进入人体后尽可能快地与其战斗。”
原始出处：
AIDS，22(12):1487-1491，Salix Boulet，Nicole F Bernard
CLINICAL SCIENCE
Abstract:
Objectives: Coexpression of certain combinations of natural killer cell receptor KIR3DL1 and HLA-B alleles is associated with slower time to AIDS. The strongest protection in terms of disease outcome in KIR3DL1 homozygotes (3DL1 hmz) is coexpression of HLA-B*57 and a set of KIR3DL1 genotypes (3DL1*h/*y) lacking alleles expressed at low levels on natural killer cells. We questioned whether this allele combination could also influence resistance to infection.
Design: The genetic distribution of 3DL1*h/*y and HLA-B*57 was compared in 41 HIV-exposed uninfected and 186 recently HIV-infected 3DL1 hmz.
Methods: KIR3DL1 subtyping was performed by sequencing the exons 3, 4, 5, 7-9. The major histocompatibility complex class IB locus was typed by sequence specific oligonucleotide PCR and sequencing to resolve Bw4 and Bw6 alleles and the amino acid present at position 80.
Results: Percentage carriers of HLA-B*57 in HIV-exposed uninfected and individuals in a primary infection cohort was 12.2 and 4.3%, respectively (P = 0.0631), whereas that of 3DL1*h/*y was similar in both populations (P = 0.221). The 3DL1*h/*y-HLA-B*57 combined genotype was more frequent in exposed uninfected individuals (12.2%) than individuals in primary infection (2.7%) (P = 0.019; odds ratio, 5.03; 95% confidence intervals, 1.38-18.3).
Conclusion: Coexpression of 3DL1*h/*y and B*57, which has been associated with a reduced risk of progressing to AIDS in HIV-infected individuals also lowers the risk of HIV infection in exposed uninfected individuals.
