INVESTIGATION OF THE POTENTIAL ROLE OF MEMBRANE CD38 IN PROTECTION AGAINST CELL-DEATH INDUCED BY HIV-1

The aim of the present study was to assess the possibility that mCD38, a bifunctional ectoenzyme with NAD(+) hydrolase and ADP ribose cyclas e activities, exerts a protective role in the development of acute, no n-syncytial cell death from HIV-1 This hypothesis was tested in a pane l of human T-cell lines with defined membrane CD4 (mCD4) expression. A negative correlation was found between the levels of mCD38 expression and the rate of acute cell death from HIV-1 observed 96 h after infec tion. The negligible rate of cell death from HN-I detected in some cel l lines (H9 and Supt-1) is apparently unrelated to the level of mCD4 e xpression, whereas the association with high levels of mCD38 is confir med. In H9 and Supt-1 cells, the fraction of cells positive to HIV-1 p 24 is lower than in the mCD38(low) cell lines (MT-4, MT-2, C8166). Thi s suggests that high CD38 expression is correlated to resistance to HI V-1 infection, resulting in a lower rate of cell death. A further find ing supporting the work hypothesis is that the addition of nicotinamid e, a reaction product of CD38, confers to MT-4 cells (mCD38(low))parti al protection against acute cell death from HIV-1. This indicates that nicotinamide may be at least partially responsible for the. correlati on observed between high level of mCD38 and negligible rates of acute cell death from HIV-1.