Down-regulation of cell surface CXCR4 by HIV-1.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Choi
Bongkun
B
Department of Microbiology and Immunology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. choib01@med.nyu.edu
Gatti
Paul J
PJ
Fermin
Cesar D
CD
Vigh
Sandor
S
Haislip
Allyson M
AM
Garry
Robert F
RF
D002460:Cell Line; D015536:Down-Regulation; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*
D019718:Receptors, CXCR4