Interferon alpha-mediated inhibition of human immunodeficiency virus type 1 provirus synthesis in T-cells

Previously, we have shown that interferon (IFN)-alpha markedly inhibits human immunodeficiency virus type-1 (HIV-1) replication in the CEM-174 lymphocytic cell line during a single replication cycle. In the present study, we demonstrate that the IFN-mediated block of HIV-1 replication is at the level of HIV-1 provirus formation. Using polymerase chain reaction and a set of primers that detects complete or nearly complete proviral DNA, HIV-1 provirus could be found as early as 5 hr after infection in CEM-174 cells and peripheral blood lymphocytes. Pretreatment of cells with 500 U/ml IFN-alpha resulted in a significant reduction in the relative levels of HIV-1 proviral DNA. The levels of HIV-1 proviral DNA in IFN-alpha-treated cells were also reduced when primers detecting the early reverse-transcripts were used, indicating that IFN interferes with the initiation of HIV-1 reverse-transcription. The inhibition of provirus formation was also observed in vitro; addition of cytoplasmic extracts from IFN-treated CEM-174 cells, but not from the control cells, resulted in inhibition of both virion-associated and recombinant HIV-1 reverse transcriptase activity. These studies implicate that, when used therapeutically, IFN-alpha should limit the spread of HIV-1 infection.