INCREASED EFFICACY OF HUMAN NATURAL INTERFERON-ALPHA (IFN-ALPHA-N3) VERSUS HUMAN RECOMBINANT IFN-ALPHA-2 FOR INHIBITION OF HIV-1 REPLICATION IN PRIMARY HUMAN MONOCYTES

Natural IFN-alpha n3, a purified mixture of many different natural IFN alpha species, was 10- to 100-fold more effective than equal concentrations of human rIFN-alpha 2b or rIFN-alpha 2a 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-alpha m3 was more effective than rIFN-alpha 2b at lower concentrations for protection against a constant HIV-1 inoculum; cells treated with natural IFN-alpha n3 were protected against a greater HIV-1 challenge than were cells treated with the same concentration of rIFN-alpha 2b. Fractionation of natural IFN-alpha n3 by reversed-phase high-pressure liquid chromatography (RP-HPLC) showed that most antiviral activity for HIV localized to discrete and reproducible peaks. The RP-NPLC peak that contained purified natural IFN-alpha 2b was the least effective fraction, These data suggest heterogeneity among IFN-alpha species for antiviral activity against HIV and may provide a molecular basis for more effective IFN-alpha therapy.