Role of the first and third extracellular domains of CXCR-4 in human immunodeficiency virus coreceptor activity
Role of the first and third extracellular domains of CXCR-4 in human immunodeficiency virus coreceptor activity
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DOI：
10.1128/jvi.71.6.4744-4751.1997
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发表时间：
1997-06-01
影响因子：
5.4
通讯作者：
Alizon, M
中科院分区：
文献类型：
--
作者：
Brelot, A;Heveker, N;Alizon, M
CXCR-4趋化因子受体和CD 4作为细胞系适应性人类免疫缺陷病毒1型和2型的共受体细胞系适应的HIV-1毒株LAI和NDR以及双嗜性HIV-2毒株ROD能够感染表达人CXCR-4的CD 4（+）细胞，而只有LAI能够感染表达大鼠CXCR-4同源物的细胞。通过使用人-大鼠CXCR-4嵌合体来解决该菌株选择性。所有测试的嵌合体介导LAI感染，但仅含有人CXCR-4的第三胞外结构域（e3）的嵌合体介导NDK和ROD感染。e3结构域可能是NDK和ROD与CXCR-4而不是LAI的功能性相互作用所需的。或者，LAI也可能与e3相互作用，但以不同的方式。抗人CXCR-4的单克隆抗体12 G5未对表达大鼠CXCR-4的细胞进行染色。嵌合的人-大鼠CXCR-4使我们能够在e3结构域中定位12 G5表位。12 G5中和某些HIV-1和HIV-2毒株感染的能力也与e3在CXCR-4辅助受体活性中的作用一致。大部分氨基末端胞外结构域（e1）的缺失消除了人CXCR-4对ROD和NDK的辅助受体活性，但对LAI没有影响。这些结果表明，HIV毒株对它们与CXCR-4的相互作用有不同的要求。它们还表明双嗜性HIV与CCR-5和CXCR-4的相互作用存在差异。
The CXCR-4 chemokine receptor and CD4 behave as coreceptors for cell line-adapted human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and for dual-tropic HIV strains, which also use the CCR-5 coreceptor, The cell line-adapted HIV-1 strains LAI and NDR and the dual-tropic HIV-2 strain ROD were able to infect CD4(+) cells expressing human CXCR-4, while only LAI was able to infect cells expressing the rat homolog of CXCR-4. This strain selectivity was addressed by using human-rat CXCR-4 chimeras, All chimeras tested mediated LAI infection, but only those containing the third extracellular domain (e3) of human CXCR-4 mediated NDK and ROD infection, The e3 domain might be required for the functional interaction of NDK and ROD, but not LAI, with CXCR-4, Alternatively, LAI might also interact with e3 but in a different way, Monoclonal antibody 12G5, raised against human CXCR-4, did not stain cells expressing rat CXCR-4. Chimeric human-rat CXCR-4 allowed us to map the 12G5 epitope in the e3 domain. The ability of 12G5 to neutralize infection by certain HIV-1 and HIV-2 strains is also consistent with the role of e3 in the coreceptor activity of CXCR-4. The deletion of most of the amino-terminal extracellular domain (e1) abolished the coreceptor activity of human CXCR-4 for ROD and NDK but not for LAI. These results indicate that HIV strains have different requirements for their interaction with CXCR-4. They also suggest differences in the interaction of dual-tropic HIV with CCR-5 and CXCR-4.