Effects of CD4 synthetic peptides on HIV type I envelope glycoprotein function.
Benzylated derivatives of a peptide (CD4(81-92)) representing the CDR3-like region of CD4 were previously found to inhibit gp120 binding, HIV-1 infectivity, and syncytium formation. These results have been interpreted to indicate a role for the corresponding CD4 region in these processes. The peptide (TbYICbEbVEDQKAcEE) is the prototype of a series of similar CD4(81-92) derivatives. We report that this peptide noncompetitively inhibits binding to CD4 of both gp120 and a mAb (MAX.16H5), both of which recognize the CDR2-like region of CD4. The binding of an antibody (Leu 3a) that is directed against a different area of the D1 domain of CD4 was also inhibited. The peptide derivative inhibited both HIV-1- and HTLV-1-mediated syncytium formation in the same concentration range. Nonbenzylated cyclic and linear peptides representing the CDR3-like region of CD4 (CD4(84-101)) had only minor effects on gp120 binding which were not sequence specific. The results of this study suggest that the effects of benzylated CD4(81-92) derivatives on HIV-1 binding or fusion should not be used to reach conclusions about the function of the corresponding CD4 region.
Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, MA 02115.
H
H
Repke
D
D
Gabuzda
G
G
Palù
F
F
Emmrich
J
J
Sodroski
D001665:Binding Sites; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments