The second extracellular loop of CXCR4 is involved in CD4-independent entry of human immunodeficiency virus type 2.
Human immunodeficiency virus type 2 (HIV-2) strains that infect cells in the absence of cellular CD4 emerge spontaneously in vitro after culture in CD4+ T-cell lines. The HIV-2ROD/B strain can use the CXCR4 chemokine receptor for efficient entry into CD4+ cells. Here we have shown that the rat homologue of CXCR4, in the absence of CD4, failed to mediate CD4-independent entry by ROD/B. Furthermore, using rat-human chimeric CXCR4 receptors we have demonstrated that the second extracellular loop (E2) of human CXCR4 is critical for HIV-2 infection of CD4+ cells. E2 is also important for HIV-1 infection of CD4+ cells. Our results therefore indicate that the role of E2 in HIV entry is conserved for HIV-1 and HIV-2 and for infection in the presence or absence of CD4.
Section of Virology, Chester Beatty Laboratories, The Institute of Cancer Research, London, UK.
J D
JD
Reeves
N
N
Heveker
A
A
Brelot
M
M
Alizon
P R
PR
Clapham
L
L
Picard
D000818:Animals; D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism / Q000502:physiology; D015498:HIV-2 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D051381:Rats; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D015704:CD4 Antigens; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins