Chemokine (C-C motif) receptor 5-using envelopes predominate in dual/mixed-tropic HIV from the plasma of drug-naive individuals
Chemokine (C-C motif) receptor 5-using envelopes predominate in dual/mixed-tropic HIV from the plasma of drug-naive individuals
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DOI：
10.1097/qad.0b013e32830184ba
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发表时间：
2008-07-31
期刊：
影响因子：
3.8
通讯作者：
Demarest, James F.
中科院分区：
文献类型：
--
作者：
Irlbeck, David M.;Amrine-Madsen, Heather;Demarest, James F.
目的：HIV-1利用CD4和趋化因子（C-C基序）受体5 （CCR5）或趋化因子（C-X-C基序）受体4 （CXCR4）进入宿主细胞。目前正在开发用于治疗HIV-1感染的小分子CCR5拮抗剂。由于HIV-1也可能使用CXCR4进入，对于携带CCR5和CXCR4（双/混合热带）病毒的患者，使用CCR5进入抑制剂是有争议的。本研究的目的是确定嗜CCR5型和嗜CXCR4型病毒在初用药患者的双/混合嗜CCR5型病毒分离株中的比例，以及使用CCR5或CXCR4或两者的病毒的表型和基因型关系。设计：14例未经抗逆转录病毒治疗的hiv -1感染患者被鉴定为具有双/混合嗜性病毒的群体共受体向性读数。对每位患者血浆病毒进行患者内共受体趋向性和env克隆基因型比较。结果：来自双/混合嗜性抗逆转录病毒患者的病毒群主要由嗜ccr5的环境克隆与嗜r5x4的环境克隆混合组成，偶尔也有嗜cxcr4的环境克隆。有趣的是，r5x4 -热带环境克隆对CXCR4的利用效率随着它们与同一患者的ccr5 -热带环境克隆的遗传关系而变化。结论：这些数据表明，这些双热带/混合热带人群中的大多数病毒使用CCR5，并提示抗逆转录病毒初始患者可能受益于包括CCR5进入抑制剂的联合治疗。(C) 2008年威科集团健康垂直条Lippincott Williams & Wilkins。
Objective: HIV-1 utilizes CD4 and either chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor 4 (CXCR4) to gain entry into host cells. Small molecule CCR5 antagonists are currently being developed for the treatment of HIV-1 infection. Because HIV-1 may also use CXCR4 for entry, the use of CCR5 entry inhibitors is controversial for patients harboring CCR5-using and CXCR4-using (dual/mixed-tropic) viruses. The goal of the present study was to determine the proportion of CCR5-tropic and CXCR4-tropic viruses in dual/mixed-tropic virus isolates from drug-naive patients and the phenotypic and genotypic relationships of viruses that use CCR5 or CXCR4 or both.Design: Fourteen antiretroviral-naive HIV-1-infected patients were identified as having population coreceptor tropism readout of dual/mixed-tropic viruses. Intrapatient comparisons of coreceptor tropism and genotype of env clones were conducted on plasma virus from each patient.Results: Viral populations from anti retroviral-naive patients with dual/mixed-tropic virus are composed primarily of CCR5-tropic env clones mixed with those that use both coreceptors (R5X4-tropic) and, occasionally, CXCR4-tropic env clones. Interestingly, the efficiency of CXCR4 use by R5X4-tropic env clones varied with their genetic relationships to CCR5-tropic env clones from the same patient.Conclusion: These data show that the majority of viruses in these dual/mixed-tropic populations use CCR5 and suggest that anti retroviral-naive patients may benefit from combination therapy that includes CCR5 entry inhibitors. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.