A tyrosine-rich region in the N terminus of CCR5 is important for human immunodeficiency virus type 1 entry and mediates an association between gp120 and CCR5.
Human immunodeficiency virus type 1 (HIV-1) requires the presence of specific chemokine receptors in addition to CD4 to enter target cells. The chemokine receptor CCR5 is used by the macrophage-tropic strains of HIV-1 that predominate during the asymptomatic stages of infection. Here we identify a small tyrosine-rich region of CCR5 proximal to the N-terminal cysteine that is critical for entry of macrophage-tropic and dual-tropic variants of HIV-1. HIV-1 infection of cells expressing CCR5 mutants with changes in this region was substantially reduced compared with the infection of cells bearing wild-type CCR5. Simian immunodeficiency virus (SIVmac239) entry was also ablated on a subset of these mutants but enhanced on others. These differences in virus entry were correlated with the relative ability of soluble, monomeric HIV-1 and SIVmac239 gp120 glycoproteins to bind the CCR5 mutants. These results identify a region of CCR5 that is necessary for the physical association of the gp120 envelope glycoprotein with CCR5 and for HIV-1 infection.
Farzan
M
M
Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Choe
H
H
Vaca
L
L
Martin
K
K
Sun
Y
Y
Desjardins
E
E
Ruffing
N
N
Wu
L
L
Wyatt
R
R
Gerard
N
N
Gerard
C
C
Sodroski
J
J
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D004285:Dogs; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009154:Mutation; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D014443:Tyrosine; D014779:Virus Replication
D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D014443:Tyrosine