AEGiS-07IAC: Role of the CDR3 region of CD4 in HIV-1 infection and cytopathogenesis defined by human- and chimpanzee-based CD4 synthetic peptides.

7th International AIDS Conference


Florence, Italy — June 16-21, 1991

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Role of the CDR3 region of CD4 in HIV-1 infection and cytopathogenesis defined by human- and chimpanzee-based CD4 synthetic peptides.

Int Conf AIDS 1991 Jun 16-21; 7:92 (abstract no. M.A.1003)
Eiden LE, Rausch DM, Kalyanaraman VS, Hwang KM, Berger EA, Lifson JD; NIMH, Bethesda, Maryland, USA

OBJECTIVE: Peptide derivatives of CD4 (81-92), a region which includes a portion of the CDR3 domain important in gp 120 binding to CD4, were synthesized, based on either the chimpanzee or human sequence. Differential ability of the two peptides to inhibit gp120 binding to CD4, HIV infection, or cell fusion could help to explain the observed differences in human and chimpanzee CD4-positive cells to support HIV infection and fusion, as well as the pathogenic sequelae of HIV infection in the two species.

METHODS: The potency of 1,4,5-tribenzyl, 10-acetyl-TYICEVEDQKEE or -TYICEVGDQKEE to inhibit HIV-1HTLVIIIB and HIV-1RF-II infection and cell fusion, and gp120 binding to CD4 were tested using previously published methods (J. Immunol. 145:4072, 1990).

RESULTS: Chimpanzee- and human-based CD4(81-92) peptides were equipotent to inhibit 125I-gp120 binding to CD4-positive cells and HIV-1 infection of CEM-SS cells (IC50 12-60 muM). The human-based CD4(81-92) peptide inhibited HIV-1 induced cell fusion at 16-32 muM, while the chimpanzee-based peptide inhibited fusion only at greater than or equal to 250 muM. The human-based peptide was also considerably more potent than the chimpanzee-based peptide to induce the release of gp120 from the surface of cells expressing the HIV-1 gp41/gp120 envelope complex.

CONCLUSIONS: The CDR3 region of CD4 is involved in HIV-1 binding to CD4, in HIV-1 infection, and in HIV-1-induced syncytium formation. Subtle differences in the structural requirements for gp120 binding occurring during HIV-1 infection compared to HIV-1-induced cell fusion have been distinguished in the CDR3 region, and may provide a partial explanation for the differences in the biology of HIV infection and pathogenesis in chimpanzee and man.

Keywords: AEGIS, Antigens, CD4, HIV Infections, Complementarity Determining Regions, Pan troglodytes, HIV-1, Peptides, Cell Fusion, Peptide Fragments, HIV-2, Giant Cells, CD4 (81-92), CDR3 region, Human, Male, Animal, ICA7KWDaegis,antigens,cd4,hivinfections,complementaritydeterminingregions,pantroglodytes,hiv-1,peptides,cellfusion,peptidefragments,hiv-2,giantcells,cd4(81-92),cdr3region,human,male,animal,ica7
910616
MA1003

Copyright © 1991 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.