Synthetic peptides allow discrimination of structural features of CD4(81-92) important for HIV-1 infection versus HIV-1-induced syncytium formation.
Benzylated peptides with a primary amino acid sequence corresponding to either human CD4(81-92) (#18), or chimpanzee CD4(81-92) (#18C), were equipotent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection of CD4+ cells and high-affinity binding of 125I-gp120 to CD4+ cells. The chimpanzee-based CD4(81-92) peptide, however, which differs from the human peptide by a single amino acid substitution (E for G) at position 87, was considerably less potent than the human CD4(81-92)-based peptide congener to inhibit HIV-1-induced cell-cell fusion. These data suggest that a portion of the CD4 molecule contained within the sequence CD4(81-92) is involved in binding gp120 during both HIV-1 infection and HIV-1-induced syncytium formation in human cells, but that the presence of a glutamic acid at position 87 in this sequence is more critical for the CD4/gp120 interaction leading to syncytium formation than for the CD4/gp120 interaction leading to primary infection of CD4-positive cells. The region CD4(81-92) may critically contribute to CD4-mediated HIV-1 pathogenesis in humans, and its alteration might explain the lack of pathogenic sequelae of HIV-1 infection in chimpanzees.
Lifson
J D
JD
Genelabs Incorporated, Redwood City, CA 94063.
Rausch
D M
DM
Kalyanaraman
V S
VS
Hwang
K M
KM
Eiden
L E
LE
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D002459:Cell Fusion; D002460:Cell Line; D015726:Giant Cells; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D010455:Peptides / Q000737:chemistry; D014779:Virus Replication
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010455:Peptides