EFFECT OF ANTIBODY TO HIV-1 TAT PROTEIN ON VIRAL REPLICATION IN-VITROAND PROGRESSION OF HIV-1 DISEASE IN-VIVO

In HIV-1-infected cell cultures, a relatively low concentration (5 mu g/ml) of monoclonal antibody (mAb) against HIV-1-transactivating Tat p rotein was an efficient inhibitor of HIV-1 replication both in HIV-1(( IIIB))-infected Jurkat cell and peripheral blood mononuclear cell (PBM C) cultures and significantly reduced the expression of a Tat-responsi ve CAT-reporter construct in HIV-1((IIIB))-infected Jurkat cells. Anti -Tat mAb also caused a significant reduction and a consistent delay in HIV-1 replication when added to PBMCs from HIV-1-infected patients co cultivated with phytohemagglutinin (PHA)stimulated normal PBMCs. These data indicate that an autocrine-paracrine loop sustained by extracell ular Tat protein, which is actively released by HIV-1-infected cells, may affect HIV-1 replication in cell cultures in vitro. An inverse rel ationship between natural anti-Tat antibody levels and p24 antigenemia was demonstrated by retrospective analysis of serial serum samples ob tained from 10 HIV-1-seropositive hemophiliac patients followed over a 7-9-year period. This datum points to a possible influence of anti-Ta t antibody on the progression of HIV-1 disease in vivo. These findings have strong implications for Tat protein as a possible target for spe cific immunotherapy in HIV-1-infected patients.