Structural interactions between chemokine receptors, gp120 Env and CD4.
Seven transmembrane segment (7TMS) receptors for chemokines and related molecules have been demonstrated to be essential, in addition to CD4, for HIV and SIV infection. The beta-chemokine receptor CCR5 is the primary, perhaps sole, co-receptor for HIV-1 during the early and chronic phases of infection and supports infection by most primary HIV-1 and many SIV isolates. Late-stage primary and laboratory-adapted HIV-1, HIV-2, and SIV isolates can use other 7TMS receptors. CXCR4 appears especially important in late-stage HIV infection; several related receptors can also be used. The specificity of SIV viruses is similar. Commonalities among these receptors, combined with analyses of mutated molecules, indicate that discrete, conformationally-dependent sites on the chemokine receptors determine their association with the third variable and conserved regions of viral envelope glycoproteins. These studies are useful for elucidating the mechanism and molecular determinants of HIV-1 entry, and of inhibitors to that entry.
Choe
H
H
Division of Human Retrovirology, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA, 02115, USA.
Martin
K A
KA
Farzan
M
M
Sodroski
J
J
Gerard
N P
NP
Gerard
C
C
D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000737:chemistry* / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011940:Receptor Aggregation; D019707:Receptors, Chemokine / Q000737:chemistry* / Q000502:physiology*; D011991:Receptors, Virus / Q000737:chemistry* / Q000502:physiology*; D014779:Virus Replication / Q000276:immunology
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019707:Receptors, Chemokine; D011991:Receptors, Virus