INTERFERON-GAMMA PROTECTS PRIMARY MONOCYTES AGAINST INFECTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Monocytes treated with 500 IU/ml human recombinant interferon-gamma (r IFN-gamma) 1 day before and continuously after human immunodeficiency virus (HIV) infection showed no evidence of virus replication 7 days a fter addition of the viral inoculum. There was no HIV-associated cytop athic effect, no reverse transcriptase (RT) activity or p24 detected i n culture fluids, and no HIV RNA or DNA in cell lysates. Furthermore, no evidence of HIV infection was evident in replicate cultures in whic h all IFN-gamma was removed at 7 days and the cells were cultured for an additional 3 weeks without IFN-gamma The 50% inhibitory dose for re duction of maximum RT activity in HIV-infected monocyte cultures was a bout 1 IU/ml IFN-gamma. No increase in HIV replication was evident in monocytes treated with IFN-gamma at any concentration (0 to 5000 IU/ml ) or at any time (7 days before to 10 days after HIV infection). In si de-by-side experiments with identical monocytes and HIV-1 stock, rIFN- gamma was 10 to 20 times more effective than rIFN-alpha 2b for inducti on of antiviral activity. With both interferons, significant antiviral activity was evident with monocytes treated 1 day before, at the time of, or up to 3 days after infection. At 7 to 10 days after infection (a time at which less than 20% of total cells were infected with HIV) addition of even high concentrations of IFN-alpha or IFN-gamma had no effect on virus replication. These data suggest that the principal act ion of IFN-alpha and IFN-gamma was directed against the fluid-phase vi rus. Cell-cell spread of infection within the HIV-infected monocyte cu lture and extent of virus replication in HIV-infected cells were not a ffected by interferon treatment.