Increased Efficacy of Human Natural Interferon α (IFN-αn3) Versus Human Recombinant IFN-α2 for Inhibition of HIV-1 Replication in Primary Human Monocytes

Abstract

Natural IFN-αn3, a purified mixture of many different natural IFNα species, was 10- to 100-fold more effective than equal concentrations of human rIFN-α2b or rIFN-α2a for inhibition of HIV replication in primary human monocytes. This difference was highly reproducible in multiple side-by-side experiments using the identical HIV-1 inoculum and the same monocyte target cells: natural IFN-αn3 was more effective than rIFN-α2b at lower concentrations for protection against a constant HIV-1 inoculum; cells treated with natural IFN-αn3 were protected against a greater HIV-1 challenge than were cells treated with the same concentration of rIFN-α2b. Fractionation of natural IFN-αn3 by reversed-phase high-pressure liquid chromatography (RP-HPLC) showed that most antiviral activity for HIV localized to discrete and reproducible peaks. The RP-HPLC peak that contained purified natural IFN-α2b was the least effective fraction. These data suggest heterogeneity among IFN-α species for antiviral activity against HIV and may provide a molecular basis for more effective IFN-α therapy.