INCREASED RATE OF HIV-1 ENTRY AND ITS CYTOPATHIC EFFECT IN CD4(+) CXCR4(+) T-CELLS EXPRESSING RELATIVELY HIGH-LEVELS OF CD26/

The role of the T-cell activation antigen CD26 was evaluated in viral entry and infection of CD4(+)/CXCR4(+) cells by the lymphotropic HIV-1 Lai isolate. For this purpose, CEM T cells, which are permissive to H IV infection and express low levels of CD26, were used to establish by transfection four groups of cell clones expressing either low, high, and very high levels of CD26, or expressing the anti-sense RNA of CD26 . Entry was monitored by the detection of proviral DNA synthesis and t he kinetics of virus production, whereas the cytopathic effect was dem onstrated by the occurrence of apoptosis. HIV entry and infection were consistently accelerated by at least 24 to 48 h in clones expressing high levels of CD26 compared to the parental cells or to the clones ex pressing low levels of CD26. Interestingly, infection of clones expres sing very high levels of CD26 was not accelerated and showed a kinetic s of infection similar to that of low CD26 expressing clones. Moreover , HN infection was significantly reduced in the clones expressing CD26 anti-sense RNA. In the different clones, apoptosis was dependent on t he severity of virus infection and occurred after the accumulation of HIV envelope glycoproteins. Our results demonstrate that with equivale ntly expressed levels of CD4 and CXCR4 in cell lines established from CEM cells, relatively high levels of CD26 contribute to an increased r ate of HIV entry, infection, and apoptosis. Furthermore, they point ou t that overexpression of CD26 in a given cell line may lead to a negat ive effect on HIV infection. Consequently, CD26 appears to regulate HI V entry and apoptosis, processes which are critical for viral pathogen esis. (C) 1998 Academic Press.