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 n3 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-HPLC 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.
Fan
S X
SX
Department of Cellular Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
Skillman
D R
DR
Liao
M J
MJ
Testa
D
D
Meltzer
M S
MS
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology; D011994:Recombinant Proteins; D014779:Virus Replication / Q000187:drug effects
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins