Redd Andrew D, Laeyendecker Oliver, Kong Xiangrong, Kiwanuka Noah, Lutalo Tom, Huang Wei, Gray Ronald H, Wawer Maria J, Serwadda David, Eshleman Susan H, Quinn Thomas C
Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, USA.
AIDS Res Hum Retroviruses. 2012 Mar;28(3):289-94. doi: 10.1089/AID.2011.0006. Epub 2011 Aug 5.
CCR5 is the primary coreceptor for HIV entry. Early after infection, the HIV viral population diversifies rapidly into a quasispecies. It is not known whether the initial efficiency of the viral quasispecies to utilize CCR5 is associated with HIV disease progression or if it changes in an infected individual over time. The CCR5 and CXCR4 utilization efficiencies (R5-UE and X4-UE) of the HIV quasispecies were examined using a pseudovirus, single-round infection assay for samples obtained from known seroconverters from Rakai district, Uganda (n=88). Initial and longitudinal R5-UE values were examined to assess the association of R5-UE with HIV disease progression using multivariate Cox proportional hazard models. Longitudinal samples were analyzed for 35 seroconverters who had samples available from multiple time points. There was no association between initial or longitudinal changes in R5-UE and the hazard of HIV disease progression (p=0.225 and p=0.942, respectively). In addition, R5-UE increased significantly over time after HIV seroconversion (p<0.001), regardless of HIV subtype or the emergence of CXCR4-tropic virus. These data demonstrate that the R5-UE of the viral quasispecies early in HIV infection is not associated with disease progression, and that R5-UE levels increase in HIV-infected individuals over time.
CCR5是HIV进入人体的主要共受体。感染后早期，HIV病毒群体迅速多样化形成准种。目前尚不清楚病毒准种最初利用CCR5的效率是否与HIV疾病进展相关，或者在感染个体中其是否会随时间发生变化。利用假病毒单轮感染试验，对从乌干达拉克伊地区已知血清转化者中获取的样本（n = 88）检测HIV准种的CCR5和CXCR4利用效率（R5-UE和X4-UE）。使用多变量Cox比例风险模型检查初始和纵向R5-UE值，以评估R5-UE与HIV疾病进展的相关性。对35名在多个时间点有可用样本的血清转化者的纵向样本进行分析。R5-UE的初始或纵向变化与HIV疾病进展风险之间均无关联（p值分别为0.225和0.942）。此外，HIV血清转化后，无论HIV亚型或CXCR4嗜性病毒的出现情况如何，R5-UE均随时间显著增加（p<0.001）。这些数据表明，HIV感染早期病毒准种的R5-UE与疾病进展无关，且HIV感染个体的R5-UE水平随时间升高。
