The CCR5 and CXCR4 coreceptors are both used by human immunodeficiency virus type 1 primary isolates from subtype C
The CCR5 and CXCR4 coreceptors are both used by human immunodeficiency virus type 1 primary isolates from subtype C
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DOI：
10.1128/jvi.77.7.4449-4456.2003
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发表时间：
2003-04-01
影响因子：
5.4
通讯作者：
Morris, L
中科院分区：
文献类型：
--
作者：
Cilliers, T;Nhlapo, J;Morris, L
从29例南非晚期艾滋病患者中分离到不同共受体使用谱的人类免疫缺陷病毒1型(HIV-1)C亚型病毒。所有24株R5分离株均被CCR5特异性药物PRO 140和RANTES抑制，而2株X4病毒和3株R5X4病毒对CXCR4特异性抑制剂AMD3100敏感。这五种X4或R5X4病毒都能在不表达CCR5的外周血单核细胞中复制。当使用共受体转染的细胞系进行测试时，一种R5病毒也能够使用CXCR6，另一种R5X4病毒可以使用CCR3、Bob/GPR15和CXCR6。与R5病毒相比，R5X4和X4病毒含有更多样化的V3环序列，具有更高的总正电荷。因此，一些HIV-1 C亚型病毒能够使用CCR5、CXCR4或同时使用CXCR4和CCR5进入，并且它们对通过这些辅助受体进入的特定抑制剂敏感。这些观察结果与了解艾滋病毒-1 C亚型在发展中国家的迅速传播以及干预和治疗战略的设计有关。
Human immunodeficiency virus type 1 (HIV-1) subtype C viruses with different coreceptor usage profiles were isolated from 29 South African patients with advanced AIDS. All 24 R5 isolates were inhibited by the CCR5-specific agents, PRO 140 and RANTES, while the two X4 viruses and the three R5X4 viruses were sensitive to the CXCR4-specific inhibitor, AMD3100. The five X4 or R5X4 viruses were all able to replicate in peripheral blood mononuclear cells that did not express CCR5. When tested using coreceptor-transfected cell lines, one R5 virus was also able to use CXCR6, and another R5X4 virus could use CCR3, BOB/GPR15, and CXCR6. The R5X4 and X4 viruses contained more-diverse V3 loop sequences, with a higher overall positive charge, than the R5 viruses. Hence, some HIV-1 subtype C viruses are able to use CCR5, CXCR4, or both CXCR4 and CCR5 for entry, and they are sensitive to specific inhibitors of entry via these coreceptors. These observations are relevant to understanding the rapid spread of HIV-1 subtype C in the developing world and to the design of intervention and treatment strategies.