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 concentr ations of human rIFN-alpha 2b or rIFN-alpha 2a for inhibition of HIV r eplication in primary human monocytes. This difference was highly repr oducible in multiple side-by-side experiments using the identical HIV- 1 inoculum and the same monocyte target cells: natural IFN-alpha m3 wa s more effective than rIFN-alpha 2b at lower concentrations for protec tion against a constant HIV-1 inoculum; cells treated with natural IFN -alpha n3 were protected against a greater HIV-1 challenge than were c ells treated with the same concentration of rIFN-alpha 2b. Fractionati on of natural IFN-alpha n3 by reversed-phase high-pressure liquid chro matography (RP-HPLC) showed that most antiviral activity for HIV local ized to discrete and reproducible peaks. The RP-NPLC peak that contain ed purified natural IFN-alpha 2b was the least effective fraction, The se data suggest heterogeneity among IFN-alpha species for antiviral ac tivity against HIV and may provide a molecular basis for more effectiv e IFN-alpha therapy.