HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry.
HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry.
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HIV-1易于获得对MARAVIROC（MVC）和其他CCR5拮抗剂的耐药性，其体外具有固有的，低水平的能力，可利用使用MVC结合的CCR5进行进入。
DOI：
10.1186/1742-4690-8-89
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发表时间：
2011-11-07
期刊：
影响因子：
3.3
通讯作者：
Gorry PR
中科院分区：
文献类型：
--
作者：
Roche M;Jakobsen MR;Ellett A;Salimiseyedabad H;Jubb B;Westby M;Lee B;Lewin SR;Churchill MJ;Gorry PR
马拉韦罗(MVC)和其他CCR5拮抗剂是HIV-1进入抑制剂，与CCR5结合并改变其构象，使CCR5不再被病毒gp120包膜(Env)糖蛋白识别。对CCR5拮抗剂的耐药性是由于HIV-1环境获得了利用CCR5药物结合构象的能力。在体外筛选HIV-1对CCR5拮抗剂的耐药性是相对困难的。然而，使用CCR5的CC1/85菌株似乎特别容易在体外获得对几种CCR5拮抗剂的耐药性，包括MVC、维维菌素和AD101。在这里，我们证明了来自亲本CC1/85株的Env本身就能够与MVC结合的CCR5产生低亲和力的相互作用。然而，这种表型只出现在表达CCR5水平很高的293-Affinofile细胞和NP2-CD4/CCR5细胞中，而在表达相对较低CCR5的TZM-b1、JC53和U87-CD4/CCR5细胞以及更常用于检测CCR5拮抗剂耐药性的PBMC中被掩盖。来源于HIV-1 CC1/85毒株的环境病毒天生能够与MVC结合的CCR5低亲和力相互作用，这有助于解释CC1/85在体外相对容易获得对CCR5拮抗剂的耐药性。在患者中检测相似的表型可以确定那些在MVC上可能处于更高的病毒学失败风险的人。
Maraviroc (MVC) and other CCR5 antagonists are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5, such that CCR5 is no longer recognized by the viral gp120 envelope (Env) glycoproteins. Resistance to CCR5 antagonists results from HIV-1 Env acquiring the ability to utilize the drug-bound conformation of CCR5. Selecting for HIV-1 resistance to CCR5-antagonists in vitro is relatively difficult. However, the CCR5-using CC1/85 strain appears to be uniquely predisposed to acquiring resistance to several CCR5 antagonists in vitro including MVC, vicriviroc and AD101. Here, we show that Env derived from the parental CC1/85 strain is inherently capable of a low affinity interaction with MVC-bound CCR5. However, this phenotype was only revealed in 293-Affinofile cells and NP2-CD4/CCR5 cells that express very high levels of CCR5, and was masked in TZM-bl, JC53 and U87-CD4/CCR5 cells as well as PBMC, which express comparatively lower levels of CCR5 and which are more commonly used to detect resistance to CCR5 antagonists. Env derived from the CC1/85 strain of HIV-1 is inherently capable of a low-affinity interaction with MVC-bound CCR5, which helps explain the relative ease in which CC1/85 can acquire resistance to CCR5 antagonists in vitro. The detection of similar phenotypes in patients may identify those who could be at higher risk of virological failure on MVC.
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影响因子：
3.7
作者：
Pugach, Pavel;Ketas, Thomas J.;Moore, John P.
通讯作者：
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影响因子：
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DOI：
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发表时间：
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作者：
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