Choi Bongkun, Gatti Paul J, Fermin Cesar D, Vigh Sandor, Haislip Allyson M, Garry Robert F
Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Virol J. 2008 Jan 11;5:6. doi: 10.1186/1743-422X-5-6.
CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled chemokine receptor family, can serve as a co-receptor along with CD4 for entry into the cell of T-cell tropic X4 human immunodeficiency virus type 1 (HIV-1) strains. Productive infection of T-lymphoblastoid cells by X4 HIV-1 markedly reduces cell-surface expression of CD4, but whether or not the co-receptor CXCR4 is down-regulated has not been conclusively determined.
Infection of human T-lymphoblastoid cell line RH9 with HIV-1 resulted in down-regulation of cell surface CXCR4 expression. Down-regulation of surface CXCR4 correlated temporally with the increase in HIV-1 protein expression. CXCR4 was concentrated in intracellular compartments in H9 cells after HIV-1 infection. Immunofluorescence microscopy studies showed that CXCR4 and HIV-1 glycoproteins were co-localized in HIV infected cells. Inducible expression of HIV-1 envelope glycoproteins also resulted in down-regulation of CXCR4 from the cell surface.
These results indicated that cell surface CXCR4 was reduced in HIV-1 infected cells, whereas expression of another membrane antigen, CD3, was unaffected. CXCR4 down-regulation may be due to intracellular sequestering of HIV glycoprotein/CXCR4 complexes.
CXC趋化因子受体4（CXCR4）是G蛋白偶联趋化因子受体家族的成员之一，它可与CD4共同作为共受体，介导亲T细胞性1型人类免疫缺陷病毒（HIV-1）X4毒株进入细胞。X4型HIV-1对T淋巴母细胞的有效感染会显著降低细胞表面CD4的表达，但共受体CXCR4是否下调尚未有定论。
HIV-1感染人T淋巴母细胞系RH9导致细胞表面CXCR4表达下调。表面CXCR4的下调与HIV-1蛋白表达的增加在时间上相关。HIV-1感染后，CXCR4在H9细胞的细胞内区室中聚集。免疫荧光显微镜研究表明，CXCR4和HIV-1糖蛋白在HIV感染的细胞中共定位。HIV-1包膜糖蛋白的诱导表达也导致CXCR4从细胞表面下调。
这些结果表明，HIV-1感染的细胞中细胞表面CXCR4减少，而另一种膜抗原CD3的表达未受影响。CXCR4下调可能是由于HIV糖蛋白/CXCR4复合物在细胞内的隔离。
