Messele T, Rinke de Wit T F, Brouwer M, Aklilu M, Birru T, Fontanet A L, Schuitemaker H, Hamann D
Ethio-Netherlands AIDS Research Project at the Ethiopian Health and Nutrition Research Institute, Addis Ababa, Ethiopia.
AIDS Res Hum Retroviruses. 2001 Mar 20;17(5):433-41. doi: 10.1089/088922201750102526.
Host factors such as increased beta-chemokine production, HIV-1 coreceptor expression level, and HIV-1 coreceptor polymorphism have been thought to influence susceptibility to HIV-1 infection. To determine the protective role of these factors in Ethiopians who remained HIV-1 uninfected, despite multiple high-risk sexual exposures, we studied 21 Ethiopian women who had been employed as commercial sex workers (CSWs) for five or more years. The HIV-1-resistant CSWs were compared with low-risk age-matched female controls who had a comparable CD4+ cell percentage and mean fluorescence intensity (MFI). Genetic polymorphism in the CCR5, CCR2b, or SDF-1 genes appeared not to be associated with resistance in the Ethiopian CSWs. Expression levels of CCR5 and CXCR4 on naive, memory, and total CD4+ T cells tended to be higher in the resistant CSWs, while the production of beta-chemokines RANTES, MIP-1alpha, and MIP-1beta by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) was lower compared with low-risk HIV-1 negative controls. In vitro susceptibility of PHA-stimulated PBMCs to primary, CCR5-restricted, Ethiopian HIV-1 isolates was comparable between resistant CSWs and low-risk controls. In vitro susceptibility was positively correlated to CD4+ cell mean fluorescence intensity and negatively correlated to CCR5 expression levels, suggesting that infection of PBMCs was primarily dependent on expression levels of CD4 and that CCR5 expression, above a certain threshold, did not further increase susceptibility. Our results show that coreceptor polymorphism, coreceptor expression levels, beta-chemokine production, and cellular resistance to in vitro HIV-1 infection are not associated with protection in high-risk HIV-1-negative Ethiopian CSWs.
诸如β趋化因子产生增加、HIV-1共受体表达水平以及HIV-1共受体多态性等宿主因素被认为会影响对HIV-1感染的易感性。为了确定这些因素在尽管有多次高危性接触但仍未感染HIV-1的埃塞俄比亚人中的保护作用，我们研究了21名从事商业性工作者（CSW）五年或更长时间的埃塞俄比亚女性。将具有HIV-1抗性的CSW与年龄匹配、CD4 +细胞百分比和平均荧光强度（MFI）相当的低风险女性对照进行比较。CCR5、CCR2b或SDF-1基因的遗传多态性似乎与埃塞俄比亚CSW的抗性无关。在具有抗性的CSW中，初始、记忆和总CD4 + T细胞上CCR5和CXCR4的表达水平往往较高，而与低风险HIV-1阴性对照相比，植物血凝素（PHA）刺激的外周血单核细胞（PBMC）产生的β趋化因子RANTES、MIP-1α和MIP-1β较低。PHA刺激的PBMC对原发性、CCR5限制的埃塞俄比亚HIV-1分离株的体外易感性在具有抗性的CSW和低风险对照之间相当。体外易感性与CD4 +细胞平均荧光强度呈正相关，与CCR5表达水平呈负相关，这表明PBMC的感染主要取决于CD4的表达水平，并且CCR5表达在一定阈值以上不会进一步增加易感性。我们的结果表明，共受体多态性、共受体表达水平、β趋化因子产生以及细胞对体外HIV-1感染的抗性与高危HIV-1阴性埃塞俄比亚CSW的保护作用无关。
