T cell activation antigen, CD26, as a cofactor for entry of HIV in CD4+ cells.
The CD4 molecule is essential for binding HIV particles, but is not sufficient for efficient viral entry and infection. The cofactor was shown to be dipeptidyl peptidase IV (DPP IV), also known as CD26. This serine protease cleaves its substrates at specific motifs; such motifs area also highly conserved in the V3 loops of HIV-1, HIV-2, and related simian isolates. Entry of HIV-1 or HIV-2 into T lymphoblastoid and monocytoid cell lines was inhibited by a specific monoclonal antibody against DPP IV or specific peptide inhibitors of this protease. Coexpression of human CD4 and CD26 in murine NIH 3T3 cells rendered them permissive to infection by HIV-1 and HIV-2. These observations could provide the basis for developing simple and specific inhibitors of HIV and open a possibility for vaccine development.
Callebaut
C
C
Unité de Virologie et Immunologie Cellulaire, UA CNRS, Institut Pasteur, Paris, France.
Krust
B
B
Jacotot
E
E
Hovanessian
A G
AG
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D002460:Cell Line; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015497:HIV-1 / Q000472:pathogenicity*; D015498:HIV-2 / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D007739:L Cells; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000502:physiology; D014357:Trypsin
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; D014357:Trypsin