Thomas Susan M, Tse Doris B, Ketner D Scott, Rochford Gemma, Meyer Daniel A, Zade David D, Halkitis Perry N, Nádas Arthur, Borkowsky William, Marmor Michael
Department of Environmental Medicine, New York University School of Medicine, NY 10016-3240, USA
AIDS. 2006 Sep 11;20(14):1879-83. doi: 10.1097/01.aids.0000244207.49123.ff.
To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms.
A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Delta32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1alpha (CCL3), MIP-1beta (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years.
Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Delta32 heterozygosity and the CCR5-59029G allele.
We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Delta32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection.
验证以下假设，即与风险持续时间较短者相比，HIV风险持续时间较长的个体对HIV-1感染的易感性会降低（通过CCR5表达来衡量），并评估CCR5表达的变化是否可由已知的基因多态性来解释。
对有男男性行为且暴露于HIV-1但未感染的男性进行横断面研究。风险持续时间根据自首次接受肛交以来自我报告的年份进行估算。通过流式细胞术测定外周血CD4+单核细胞和T细胞上的CCR5表达。通过聚合酶链反应分析CCR5-Delta32突变、CCR5启动子和CCR2中的多态性以及CCL3L1的拷贝数。还测量了血浆中MIP-1α（CCL3）、MIP-1β（CCL4）和RANTES（CCL5）的水平。由于风险持续时间随年龄变化，分析仅限于67名年龄在30至49岁之间的个体。
在对年龄和种族进行调整的多元线性回归分析中，HIV风险持续时间与单核细胞上的CCR5表达之间存在显著的负相关（P = 0.01），在另一个单独模型中，与T细胞上的CCR5表达也存在类似的负相关（P = 0.03）。低CCR5表达主要归因于CCR5-Delta32杂合性和CCR5-59029G等位基因。
我们证实了CCR5表达降低在HIV-1抗性中的作用。CCR5-Delta32杂合性和CCR5-59029G等位基因是低CCR5表达的重要预测指标。尽管HIV风险持续时间长但仍抵抗感染的高CCR5表达个体构成了一个有趣的群体，可在其中寻找抵抗HIV感染的其他机制。
