THE IMMUNOSUPPRESSIVE PEPTIDE OF HIV-1 - FUNCTIONAL DOMAINS AND IMMUNE-RESPONSE IN AIDS PATIENTS

Objectives: To study the biological properties of the immunosuppressiv e peptide (ISU-peptide) of HIV-1, a 17-mer corresponding to the amino- acid domain 583-599 of the transmembrane glycoprotein gp41 of HIV-1. T his peptide exhibits sequence homology to the highly conserved ISU-pep tide of type C and D retroviruses. Also, to study the immune response against the corresponding gp41 epitope in AIDS patients. Design: The I SU-peptide and control peptides were synthesized and tested for immuno suppressive activity in different in vitro lymphocyte proliferation as says. Antibody responses were tested using a peptide enzyme-linked imm unosorbent assay. A new property of the ISU-peptide, inhibition of HIV -1 replication, was investigated using a cytopathogenicity assay. Resu lts: The ISU-peptide of HIV-1 and the immunosuppressive peptides of ty pe C and type D retroviruses possess similar functional properties. Th ey inhibit mitogen-induced and lymphokine-dependent T-lymphocyte proli feration, they are interspecies-reactive, they must be conjugated to a carrier protein in order to be immunosuppressive, and their N-termina l octamers represent the minimal immunosuppressive domain. HIV-infecte d individuals develop antibodies against an epitope located at the C-t erminal end of the ISU-peptide and the number of responders and antibo dy titres decrease during progression to AIDS. In addition to its immu nosuppressive activity, the ISU-peptide of HIV-1 inhibits the cytopath ic effect of HIV-1 on human MT4 cells, suggesting interference with vi rus replication. Conclusions: The immunosuppressive property of the IS U-peptide suggests that gp41 might contribute to the development of AI DS. The evolutionary conservation of the immunosuppressive domain and the ability of the corresponding ISU-peptide to inhibit HIV replicatio n suggest that this domain plays an important role in the life cycle o f HIV-1.