Amplification of the inflammatory cellular redox state by human immunodeficiency virus type 1-immunosuppressive Tat and gp160 proteins

In the course of our studies on oxidative stress as a component of patholog ical processes in humans, we showed th:lt microintrusion into cells with mi crocapillary and ultramicroelectrochemical detection could mimic many types of mechanical intrusion leading to an instant (0.1 s) and high (some femto moles) burst release of H2O2. Specific inhibitors of NADPH enzymes seem to support the assumption that this enzyme is one of the main targets of our e xperiments. Also, human immunodeficiency virus type 1 (HIV-1) gp160 inhibit s the cooperative response of uninfected T cells as well as Tat protein rel ease by infected cells does. In this study, we analyzed in real time, lymph ocyte per lymphocyte, the T-cell response following activation in relation to the redox state. We showed that the immunosuppressive effects of HIV-1 T at and gp160 proteins and oxidative stress are correlated, since the native but not the inactivated Tat and gp160 proteins inhibit the cellular immune response and enhance oxidative stress. These results are consistent with a role of the membrane NADPH oxidase in the cellular response to immune acti vation.