AEGiS-11IAC: The implication of CD26 in HIV infection: viral entry and its cytopathic effect.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

The implication of CD26 in HIV infection: viral entry and its cytopathic effect.

Int Conf AIDS 1996 Jul 7-12; 11:56 (abstract no. Mo.A.1002)
Callebaut C, Jacotot E, Krust B, Hovanessian AG; Institut Pasteur, UA CNRS Paris. Fax: 33 1 4061 3012. E-mail: chrcall@pasteur.fr.

OBJECTIVE: The T cell activation antigen CD26 is a cell surface serine-exopeptidase charaterized by a dipeptidyl peptidase IV (DPP IV) activity. We have previously reported that CD26 through a potential interaction with the V3 loop of HIV envelope gp120, could serve as a cofactor of CD4 in entry of lymphotropic HIV-1 Lai and HIV-2 EHO isolates. Recently, the role of CD26 along with the V3 loop was emphasized for entry and its cytopathic effect using monotropic HIV-1 isolates (Oravecz et al., 1995; Nature Medicine 1, 919); and on the other hand, a V3 loop peptide was shown to bind a synthetic CD26 peptide containing a catalytic domain involved in the DPP IV activity (Chin et al., 1995; Immun. Letters 44, 25).

METHODS: Because of the existence of species specific restrictions on HIV entry and replication, the role of CD26 or any other cofactor has to be demonstrated in human cells. However, as almost all CD4+ cells permissive to HIV infection express low but reproducibly detectable levels of CD26, we selected two such cells, CEM and Jurkat, in order to establish by transfection cell lines expressing enhanced levels of CD26. The entry was monitored by the detection of proviral DNA synthesis and by the kinetics of virus production, whereas initiation of cell death by apoptosis was monitored by infection of the different cell lines with a vaccinia virus recombinant expressing HIV gp120/gp41 complex (VV-env).

RESULTS: The entry of HIV-1 Lai was found to be accelerated by 24-48 hr in six independent clones of CEM cells expressing enhanced levels of CD26 compared with six other corresponding control clones. As a consequence of different kinetics of infection in low and high CD26 expressing CEM cells, the occurrence of cell death was at least two days earlier in high CD26 expressing cells. In a separate set of experiment using Jurkat cell lines, we could demonstrate that after 16 hr of infection with VV-env, the HIV gp120/gp41 induced apoptosis was observed only in cell lines expressing enhanced levels of CD26.

CONCLUSIONS: These results indicate that the level of CD26 could determine the rate of viral entry and its cytopathic effect, 2 events which are initiated by the interaction of gp120/gp41 complex with cell-surface CD4.

Keywords: AEGIS, Antigens, CD26, HIV Infections, HIV-1, Antigens, CD4, HIV-2, Virus Replication, Cell Line, Apoptosis, Cell Death, Human, virology, ICA11

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