Olivieri Kevin, Scoggins Robert M, Bor Yeou-cherng, Matthews Aprille, Mark David, Taylor James R, Chernauskas David, Hammarskjöld Marie-Louise, Rekosh David, Camerini David
Department of Microbiology and Myles H. Thaler Center for AIDS and Human Retrovirus Research, University of Virginia, Charlottesville, VA 22908, USA.
Virology. 2007 Feb 5;358(1):23-38. doi: 10.1016/j.virol.2006.08.027. Epub 2006 Sep 26.
Late stage AIDS associated CCR5 tropic HIV-1 clones (R5-AIDS HIV-1) exhibit greater cytopathic effects (CPE) than earlier isolates from the same patients. In this study, envelopes from a series of three biological clones derived from the same patient were evaluated as a cytopathic determinant of R5-AIDS HIV-1 for thymocytes. In a single round of replication in thymocytes, the AIDS associated clone mediated greater initiation of reverse transcription. This enhancement was not due to broadened coreceptor tropism, as all clones studied were exclusively R5 tropic. The full-length R5-AIDS env mediated greater infectivity than R5 pre-AIDS env when used to pseudotype a reporter virus. R5-AIDS env pseudotypes were more resistant to TAK-779 and showed more rapid infection kinetics but similar resistance to a CD4 blocking mAb. We conclude that the enhanced thymic replication and CPE shown by the R5-AIDS clone is due to enhanced efficiency of Env-mediated entry via CCR5.
晚期艾滋病相关的CCR5嗜性HIV-1克隆（R5-艾滋病HIV-1）比来自同一患者的早期分离株表现出更强的细胞病变效应（CPE）。在本研究中，对来自同一患者的一系列三个生物学克隆的包膜进行了评估，以确定其作为R5-艾滋病HIV-1对胸腺细胞的细胞病变决定因素。在胸腺细胞的单轮复制中，艾滋病相关克隆介导了更强的逆转录起始。这种增强并非由于共受体嗜性的拓宽，因为所有研究的克隆均为单一的R5嗜性。当用于假型化报告病毒时，全长R5-艾滋病env介导的感染性比R5艾滋病前期env更强。R5-艾滋病env假型对TAK-779更具抗性，显示出更快的感染动力学，但对CD4阻断单克隆抗体的抗性相似。我们得出结论，R5-艾滋病克隆所显示的胸腺复制增强和CPE增强是由于Env介导的通过CCR5进入的效率提高。
