CD4-independent infection by human immunodeficiency virus type 2 strain ROD/B: the role of the N-terminal domain of CXCR-4 in fusion and entry.
The human immunodeficiency virus type 2 (HIV-2) strain ROD/B can efficiently use the 7tm chemokine receptor CXCR-4 as a primary receptor to enter CD4-negative cells. We have stably expressed CXCR-4 on mink lung Mv-1-lu and feline kidney CCC cells (normally restrictive to HIV entry) and have shown efficient fusion, entry, and replication of ROD/B. Mutation of the two N-linked glycosylation sites on CXCR-4 (N11-->I, and N176-->Q) or pretreatment of CCC or Mv-1-lu cells expressing wild-type CXCR-4 with the glycosylation inhibitor tunicamycin increased fusion and entry by ROD/B. Deletion of portions of the N terminus of CXCR-4 resulted in a 3- to 10-fold decrease in cell-free infection by ROD/B and complete inhibition of cell-cell fusion by both ROD/B and another HIV-2 strain, CBL23. These data suggest that the N-terminal domain of CXCR-4 is involved in but is not essential for the efficient fusion of ROD/B with CD4-negative cells. Deletion of the C-terminal (intracellular) domain of CXCR-4 did not significantly affect entry by ROD/B, indicating that intracellular signalling through this domain does not play a significant role in entry by HIV-2.
Potempa
S
S
Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
Picard
L
L
Reeves
J D
JD
Wilkinson
D
D
Weiss
R A
RA
Talbot
S J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000502:physiology; D002415:Cats; D002459:Cell Fusion; D002478:Cells, Cultured; D006031:Glycosylation / Q000187:drug effects; D015498:HIV-2 / Q000254:growth & development*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D008907:Mink; D008969:Molecular Sequence Data; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000382:microbiology*; D014415:Tunicamycin / Q000494:pharmacology
D015704:CD4 Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D014415:Tunicamycin