Role of the amino-terminal extracellular domain of CXCR-4 in human immunodeficiency virus type 1 entry.
We have studied the role of the N-terminal extracellular domain of the human immunodeficiency virus type 1 (HIV-1) coreceptor, CXCR-4, in the entry and fusion of syncytium-inducing strains of HIV-1. Progressive deletions were introduced in the N-terminal extracellular domain of CXCR-4 and the effect on infection by different isolates was tested. Infection of cells expressing the different CXCR-4 deletion mutants by HIV-1 LAI and 89.6 was reduced only about twofold. In contrast, the HIV-1 GUN-1 and RF isolates were substantially more impaired in their ability to mediate cell-free infection and cell-cell fusion. Since LAI and RF are T-cell line-tropic viruses while 89.6 and GUN-1 are dual tropic, no clear correlation between tropism and requirements for CXCR-4 N-terminal sequences emerged. We also introduced point mutations at the two N-linked glycosylation sites. The isolates tested (LAI, RF, GUN-1, and 89.6) were not affected by the removal of predicted N-linked glycosylation sites in CXCR-4. We conclude that distinct virus strains interact differently with the CXCR-4 coreceptor and that the N-terminal extracellular domain is not the sole functional domain important for HIV-1 entry.
Picard
L
L
Chester Beatly Laboratories, Institute of Cancer Research, London, United Kingdom. laurent@icr.ac.uk
Wilkinson
D A
DA
McKnight
A
A
Gray
P W
PW
Hoxie
J A
JA
Clapham
P R
PR
Weiss
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002415:Cats; D002460:Cell Line; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV