CD4-independent infection by HIV-2 is mediated by fusin/CXCR4.
Several members of the chemokine receptor family have been shown to function in association with CD4 to permit HIV-1 entry and infection. However, the mechanism by which these molecules serve as CD4-associated cofactors is unclear. In the present report, we show that one member of this family, termed Fusin/ CXCR4, is able to function as an alternative receptor for some isolates of HIV-2 in the absence of CD4. This conclusion is supported by the finding that (1) CD4-independent infection by these viruses is inhibited by an anti-Fusin monoclonal antibody, (2) Fusin expression renders human and nonhuman CD4-negative cell lines sensitive to HIV-2-induced syncytium induction and/or infection, and (3) Fusin is selectively down-regulated from the cell surface following HIV-2 infection. The finding that one chemokine receptor can function as a primary viral receptor strongly suggests that the HIV envelope glycoprotein contains a binding site for these proteins and that differences in the affinity and/or the availability of this site can extend the host range of these viruses to include a number of CD4-negative cell types.
Endres
M J
MJ
Hematology-Oncology Division, University of Pennsylvania, Philadelphia 19104, USA.
Clapham
P R
PR
Marsh
M
M
Ahuja
M
M
Turner
J D
JD
McKnight
A
A
Thomas
J F
JF
Stoebenau-Haggarty
B
B
Choe
S
S
Vance
P J
PJ
Wells
T N
TN
Power
C A
CA
Sutterwala
S S
SS
Doms
R W
RW
Landau
N R
NR
Hoxie
J A
JA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000821:virology; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002459:Cell Fusion / Q000187:drug effects; D006224:Cricetinae; D015536:Down-Regulation; D014644:Genetic Variation; D015498:HIV-2 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008214:Lymphocytes / Q000821:virology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011784:Quail; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D011994:Recombinant Proteins