Owman C, Garzino-Demo A, Cocchi F, Popovic M, Sabirsh A, Gallo R C
Section of Molecular Neurobiology, Wallenberg Neuroscience Center, University of Lund, S-22362 Lund, Sweden.
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9530-4. doi: 10.1073/pnas.95.16.9530.
The recently cloned human chemoattractant receptor-like (CMKRL)1, which is expressed in vivo in CD4-positive immune cells, has structural homology with the two chemokine receptors C-C chemokine receptor (CCR)5 and C-X-C chemokine receptor (CXCR)4, which serve as the major coreceptors necessary for fusion of the HIV-1 envelope with target cells. In view of the structural similarity, CMKRL1 was tested for its possible function as another HIV-1 coreceptor after stable expression in murine fibroblasts bearing the human CD4 receptor. The cells were infected with 10 primary clinical isolates of HIV-1, and entry was monitored by semiquantitative PCR of viral DNA. The efficiency of the entry was compared with the entry taking place in CD4-positive cells expressing either CCR5 or CXCR4. Seven of the isolates used CMKRL1 for viral entry; they were mainly of the syncytium-inducing phenotype and also used CXCR4. Entry efficiency was higher with CMKRL1 than with CXCR4 for more than half of these isolates. Three of the ten isolates did not use CMKRL1; instead, entry was mediated by both CCR5 and CXCR4. The experiments thus indicate that CMKRL1 functions as a coreceptor for the entry of HIV-1 into CD4-positive cells. In the course of this study, leukotriene B4 was shown to be the natural ligand for this receptor (now designated BLTR), which therefore represents a novel type of HIV-1 coreceptor along with the previously identified chemokine receptors. BLTR belongs to the same general chemoattractant receptor family as the chemokine receptors but is structurally more distant from them than are any of the previously described HIV-1 coreceptors.
最近克隆出的人趋化因子受体样（CMKRL）1在体内CD4阳性免疫细胞中表达，它与两种趋化因子受体——C-C趋化因子受体（CCR）5和C-X-C趋化因子受体（CXCR）4在结构上具有同源性，而这两种受体是HIV-1包膜与靶细胞融合所必需的主要共受体。鉴于结构上的相似性，在稳定表达人CD4受体的鼠成纤维细胞中对CMKRL1作为另一种HIV-1共受体的可能功能进行了检测。用10株HIV-1的原代临床分离株感染这些细胞，并通过病毒DNA的半定量PCR监测病毒进入情况。将病毒进入的效率与在表达CCR5或CXCR4的CD4阳性细胞中发生的病毒进入效率进行比较。7株分离株利用CMKRL1进行病毒进入；它们主要是合胞体诱导型，也利用CXCR4。对于这些分离株中的一半以上，CMKRL1介导的病毒进入效率高于CXCR4。10株分离株中有3株不利用CMKRL1；相反，病毒进入是由CCR5和CXCR4共同介导的。因此，这些实验表明CMKRL1作为HIV-1进入CD4阳性细胞的共受体发挥作用。在本研究过程中，白三烯B4被证明是该受体（现命名为BLTR）的天然配体，因此它与先前鉴定的趋化因子受体一样，代表了一种新型的HIV-1共受体。BLTR与趋化因子受体属于同一类一般的趋化因子受体家族，但在结构上与它们的距离比任何先前描述的HIV-1共受体与趋化因子受体的距离更远。
