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.
Shirazi
Y
Y
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
Pitha
P M
PM
D001483:Base Sequence; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000187:drug effects* / Q000302:isolation & purification; D012367:RNA, Viral / Q000032:analysis; D013601:T-Lymphocytes / Q000382:microbiology; D014158:Transcription, Genetic / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
D016898:Interferon-alpha; D012367:RNA, Viral