Activity of superior interferon α against HIV-1 in severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes

Background Interferon (IFN) can inhibit human immunodeficiency virus type 1 (HIV-1) replication in vitro and in clinic. However, IFN therapy for HIV infection was limited by its moderate antiviral efficacy and its frequent adverse effects. In the present study we evaluated the anti-HIV efficacy of a novel synthesized superior interferon alpha (sIFN alpha). Methods We performed in vitro experiments with HIV-1 IIIB infected MT4 cells, and evaluated in vivo anti-HIV efficacy of sIFN alpha in severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice). Results We found that the 50% effective concentrations (EC50) of sIFN alpha against the replication of HIV-1 in MT4 cells was 0.06 ng/ml, representing stronger antiviral activity than interferon-alpha in vitro. In the hu-PBL-SCID mice, a dose-dependent protection pattern was observed: with 0.45 mu g and 1.35 mu g sIFN alpha daily treatments, parts of SCID mice were protected from HIV infection, whereas 2.25 mu g sIFN alpha daily treatments resulted in a terminally complete protection. Conclusions sIFN alpha shows good anti-HIV activity both in vitro and in SCID mice, may be a promising anti-HIV agent deserving clinical investigation, especially considering the potential of IFN-alpha to inhibit HIV replication in patients infected with drug-resistant variants or co-infected with hepatitis C virus (HCV). Chin Med J 2011;124(3):396-400