Interferon treatment inhibits the replication of simian immunodeficiency virus at an early stage: evidence for a block between attachment and reverse transcription.

Interferon (IFN) dramatically reduces both SIV and HIV-1 replication in vitro. However, we previously found that whereas IFN treatment of SIV-infected cells results in a decrease in the level of viral RNA, IFN treatment of HIV-1-infected cells has no effect on viral RNA expression but rather leads to a decrease in viral protein stability and a deregulation of polyprotein processing (M. B. Agy, R. L. Acker, C. H. Sherbert, and M.G. Katze, Virology 214, 379-386, 1995). To more closely define the stage of SIV replication adversely affected by IFN, we used several approaches, including PCR amplification, to examine the effects of IFN on viral DNA synthesis and integration in MT4 and 174 x CEM cells synchronously infected with SIV. Unexpectedly, we found that IFN blocked the synthesis of viral DNA in SIV-infected cells but appeared to have no effect on HIV-1 DNA synthesis. Using a p27 ELISA, we demonstrated that IFN had no effect on the attachment of SIV to MT4 cells. Thus, our results indicate that IFN blocks an early stage of SIV replication, at a step between attachment and reverse transcription. To our knowledge this is the first report to examine the effects of IFN on discrete stages of the SIV life cycle.