Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle.
In this study, we have analyzed the effect of human alpha interferon (IFN-alpha) on a single replication cycle of human immunodeficiency virus type 1 (HIV-1) infection in the lymphocytic cell line CEM-174, which is highly sensitive to the antiviral effects of IFN. Pretreatment of cells with 50 to 500 U of recombinant human IFN-alpha per ml resulted in a marked reduction in viral RNA and protein synthesis. The effect of IFN-alpha was dose dependent and was amplified in multiple infection cycles. IFN-induced inhibition of viral protein synthesis could be detected only when cells were treated with IFN-alpha prior to infection or when IFN-alpha was added up to 10 h postinfection, but not if IFN-alpha was added at the later stages of HIV-1 replication cycle or after the HIV-1 infection was already established. Analysis of the integrated HIV-1 provirus showed a marked decrease in the levels of proviral DNA in IFN-treated cells. Thus, in contrast to the previous studies on established HIV-1 infection in T cells, in which the IFN block appeared to be at the posttranslational level, during de novo infection, IFN-alpha interferes with an early step of HIV-1 replication cycle that occurs prior to the integration of the proviral DNA. These results indicate that the early IFN block of HIV-1 replication, which has been previously observed only in primary marcophages, can also be detected in the IFN-sensitive T cells, indicating that the early IFN block is not limited to macrophages.
Shirazi
Y
Y
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
Pitha
P M
PM
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D002478:Cells, Cultured; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D011994:Recombinant Proteins; D012191:Retroviridae Proteins / Q000096:biosynthesis / Q000378:metabolism; D013997:Time Factors; D016662:Virus Integration / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D007370:Interferon Type I; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D015088:2',5'-Oligoadenylate Synthetase