T Cell Activation Antigen, CD26, as a Cofactor for Entry of HIV in CD4 ⁺ Cells

Abstract

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.

Pseudopeptide TASP Inhibitors of HIV Entry Bind Specifically to a 95-kDa Cell Surface Protein

“…By biochemical approaches, different cell surface proteins have been reported to interact with the V3 loop of gp120 (15)(16)(17)(18)(19)(20) and gp41 (21)(22)(23)(24); however, in most cases the relationship between the interaction and a putative role in HIV infection has not been determined. We have previously reported that CD26, through a potential interaction with the V3 loop, may serve as a cofactor of HIV entry (25)(26)(27). Using other experimental approaches, several groups initially were not able to produce similar results; their criticisms with our response have been published (28 -32).…”

Multibranched V3 peptides inhibit human immunodeficiency virus infection in human lymphocytes and macrophages

“…More recently, it has been proposed that CDR3 synthetic peptides (28) or anti-CDR3 monoclonal antibodies (3) are able to inhibit the replication of HIV-1 after integration of the provirus. In our current model for the mechanism of action of V3 SPCs, the interaction between HIV envelope glycoproteins and the surface of CD4+ T lymphocytes and macrophages may involve the CDR3 region of CD4, and/or a distinct coreceptor (e.g., a cell surface protease), as previously postulated (6,26). The interaction between the potential coreceptors and the V3 loop could be inhibited by V3 SPCs.…”

Enhancement of antigen-induced T-cell proliferation by soluble CD26/dipeptidyl peptidase IV.

“…With regard to function, CD26 is a binding or carrier protein for adenosine deaminase (12), an enzyme whose deficiency is strongly associated with severe combined immunodeficiency disease (31). Further, it has been suggested that CD26 is a putative coreceptor for human immunodeficiency virus (32 …”