Modest human immunodeficiency virus coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor
Modest human immunodeficiency virus coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor
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DOI：
10.1128/jvi.01941-06
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Schols, Dominique
中科院分区：
文献类型：
--
作者：
Hatse, Sigrid;Huskens, Dana;Schols, Dominique
趋化因子受体CXCR3对几种人类免疫缺陷病毒1型（HIV-1）和HIV-2株及临床分离株表现出弱的辅助受体功能。这些病毒在U87.CD4细胞中产生显微镜可见的细胞病变。CXCR3细胞培养，而未转染（CXCR3阴性）U87。CD4细胞未被感染。根据特定的病毒，CXCR3的辅助受体效率比CXCR4低100到100万倍。通过在CXCR3受体300和304号位置同时进行赖氨酸到丙氨酸和丝氨酸到谷氨酸的替换，构建了携带CXCR4结合袋的CXCR3变体。该突变受体（CXCR3[K300A, S304E]）与野生型受体（CXCR3[WT]）相比，表现出明显增强的HIV共受体功能。此外，CXCR4拮抗剂AMD3100在U87.CD4细胞中表现出拮抗和抗hiv活性。CXCR3[K300A， S304E]细胞而非U87.CD4细胞。CXCR3 (WT)细胞。
The chemokine receptor CXCR3 can exhibit weak coreceptor function for several human immunodeficiency virus type 1 (HIV-1) and HIV-2 strains and clinical isolates. These viruses produced microscopically visible cytopathicity in U87.CD4.CXCR3 cell cultures, whereas untransfected (CXCR3-negative) U87.CD4 cells remained uninfected. Depending on the particular virus, the coreceptor efficiency of CXCR3 was 100- to > 10,000-fold lower compared to that of CXCR4. A CXCR3 variant carrying the CXCR4 binding pocket was constructed by simultaneous lysine-to-alanine and serine-to-glutamate substitutions at positions 300 and 304 of the CXCR3 receptor. This mutant receptor (CXCR3[K300A, S304E]) showed markedly enhanced HIV coreceptor function compared to the wild-type receptor (CXCR3[WT]). Moreover, the CXCR4 antagonist AMD3100 exhibited antagonistic and anti-HIV activities in U87.CD4.CXCR3[K300A, S304E] cells but not in U87.CD4.CXCR3[WT] cells.