Dept of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA) at Academic Medical Center of University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Virology. 2011 Apr 10;412(2):269-77. doi: 10.1016/j.virol.2011.01.010. Epub 2011 Feb 4.
During the course of at least 50% of HIV-1 subtype B infections, CCR5-using (R5) viruses evolve towards a CXCR4-using phenotype. To gain insight in the transition from CCR5 to CXCR4 coreceptor use, we investigated whether acquisition of CXCR4 use in vitro of R5 viruses from four patients resembled this process in vivo. R5 variants from only one patient acquired CXCR4 use in vitro. These variants had envelopes with higher V3 charge and higher number of potential N-linked glycosylation sites when compared to R5 variants that failed to gain CXCR4 use in vitro. In this patient, acquisition of CXCR4 use in vitro and in vivo was associated with multiple mutational patterns not necessarily involving the V3 region. However, changes at specific V3 positions were prerequisite for persistence of CXCR4-using variants in vivo, suggesting that positive selection targeting the V3 loop is required for emergence of CXCR4-using variants during natural disease course.
在至少 50%的 HIV-1 亚型 B 感染过程中，使用 CCR5 的（R5）病毒会朝着使用 CXCR4 的表型进化。为了深入了解从 CCR5 向 CXCR4 核心受体使用的转变，我们研究了来自四位患者的体外 R5 病毒是否获得了 CXCR4 使用，是否类似于体内的这一过程。只有一位患者的 R5 变体在体外获得了 CXCR4 使用。与未能在体外获得 CXCR4 使用的 R5 变体相比，这些变体的包膜具有更高的 V3 电荷和更多的潜在 N 连接糖基化位点。在该患者中，体外和体内获得 CXCR4 使用与多种突变模式相关联，不一定涉及 V3 区域。然而，特定 V3 位置的变化是体内持续存在 CXCR4 使用变体的先决条件，这表明针对 V3 环的正选择是自然疾病过程中出现 CXCR4 使用变体所必需的。
