Fowke K R, Dong T, Rowland-Jones S L, Oyugi J, Rutherford W J, Kimani J, Krausa P, Bwayo J, Simonsen J N, Shearer G M, Plummer F A
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
AIDS Res Hum Retroviruses. 1998 Nov 20;14(17):1521-30. doi: 10.1089/aid.1998.14.1521.
A small group of women (n = 80) within the Nairobi-based Pumwani Sex Workers Cohort demonstrates epidemiologic resistance to HIV-1 infection. Chemokine receptor polymorphisms and beta-chemokine overproduction have been among the mechanisms suggested to be responsible for resistance to HIV-1 infection. This study attempts to determine if any of those mechanisms are protecting the HIV-1-resistant women. Genetic analysis of CCR5 and CCR3 from the resistant women demonstrated no polymorphisms associated with resistance. Expression levels of CCR5 among the resistant women were shown to be equivalent to that found in low-risk seronegative (negative) controls, while CXCR4 expression was greater among some of the resistant women. In vitro infection experiments showed that phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from resistant women were as susceptible to infection to T cell- and macrophage-tropic North American and Kenyan HIV-1 isolates as were the PBMCs from negative controls. No significant difference in circulating plasma levels of MIP-1alpha and MIP-1beta were found between the resistant women and negative or HIV-1-infected controls. In vitro cultures of media and PHA-stimulated PBMCs indicated that the resistant women produced significantly less MIP-1alpha and MIP-1beta than did negative controls and no significant difference in RANTES levels were observed. In contrast to studies in Caucasian cohorts, these data indicate that CCR5 polymorphisms, altered CCR5 and CXCR4 expression levels, cellular resistance to in vitro HIV-1 infection, and increased levels of beta-chemokine production do not account for the resistance to HIV-1 infection observed among the women of the Pumwani Sex Workers Cohort.
内罗毕普姆瓦尼性工作者队列中的一小群女性（n = 80）表现出对HIV-1感染的流行病学抗性。趋化因子受体多态性和β趋化因子过量产生被认为是导致对HIV-1感染产生抗性的机制之一。本研究试图确定这些机制中是否有任何一种在保护这些对HIV-1有抗性的女性。对这些抗性女性的CCR5和CCR3进行基因分析，未发现与抗性相关的多态性。抗性女性中CCR5的表达水平与低风险血清阴性（阴性）对照组中的水平相当，而一些抗性女性中CXCR4的表达更高。体外感染实验表明，来自抗性女性的植物血凝素（PHA）刺激的外周血单核细胞（PBMC）对T细胞嗜性和巨噬细胞嗜性的北美和肯尼亚HIV-1分离株的感染敏感性与阴性对照的PBMC相同。抗性女性与阴性或HIV-1感染对照之间的循环血浆中MIP-1α和MIP-1β水平没有显著差异。对培养基和PHA刺激的PBMC进行体外培养表明，抗性女性产生的MIP-1α和MIP-1β明显少于阴性对照，且RANTES水平未观察到显著差异。与白种人队列研究不同，这些数据表明，CCR5多态性、CCR5和CXCR4表达水平的改变、细胞对体外HIV-1感染的抗性以及β趋化因子产生水平的增加并不能解释在普姆瓦尼性工作者队列女性中观察到的对HIV-1感染的抗性。
