The interaction of CD4 with HIV-1 gp120.
CD4 is an integral cell surface glycoprotein that is able to enhance T cell specific antigen responses when it interacts with its physiological ligand, class II major histocompatibility (MHC) molecules. In addition, CD4 is a specific cell-surface receptor for the human immunodeficiency virus-1 (HIV-1). Infection by HIV-1 is initiated by the binding of the envelope glycoprotein, gp120, to the first domain of CD4. The binding of CD4 to class II MHC is inhibited by gp120, one possible mechanism for immunosuppression in AIDS patients. In addition, the CD4/gp120 interaction may directly inhibit T cell function. Recently we have synthesized small molecules (CPFs) that specifically inhibit this interaction. CPFs bind to gp120 and prevent the binding of gp120 to CD4, and also inhibit the infectivity of HIV-1.
Silberman
S L
SL
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115.
Goldman
S J
SJ
Mitchell
D B
DB
Tong
A T
AT
Rosenstein
Y
Y
Diamond
D C
DC
Finberg
R W
RW
Schreiber
S L
SL
Burakoff
S J
SJ
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001665:Binding Sites; D015704:CD4 Antigens / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010716:Phosphatidylinositols / Q000032:analysis
D000998:Antiviral Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D000949:Histocompatibility Antigens Class II; D010716:Phosphatidylinositols