Acid lability is not an intrinsic property of interferon-alpha induced by HIV-infected cells.
Human immunodeficiency virus (HIV)-infected cells induce acid-labile interferon-alpha (al-IFN-alpha) in cultures of mononuclear cells from peripheral human blood. We have investigated the physiochemical properties of such preparations to elucidate the reasons for acid-lability of this IFN. Al-IFN-alpha is a mixture of both glycosylated and unglycosylated molecules as shown by separation on Concanavalin-A Sepharose. Acid-lability is associated only with glycosylated molecules. Upon chromatography of the glycosylated fraction on Sepharose coupled to IFN-alpha-specific antibody, the portion of the IFN that is retained and eluted with guanidine-HCl is acid-stable, whereas the excluded antiviral activity is acid-labile, and is partially neutralized by antibodies to either IFN-alpha or IFN-gamma. Also, upon further purification of the unglycosylated fraction on the same antibody column, all antiviral activity remains indistinguishable from conventional IFN-alpha. Reconstitution experiments showed that glycosylated material excluded from the anti-IFN-alpha column potentiates antiviral activity of the IFN that is specifically retained by the column. This potentiation is abolished by acid treatment. Similar results are obtained with al-IFN-alpha from the serum of acquired immunodeficiency syndrome (AIDS) patients, indicating that its acid-lability is also the consequence of an acid-labile component that is capable of enhancing the antiviral activity. The potentiation of antiviral activity obtained by combining recombinant preparations of IFN-alpha and IFN-gamma suggests that the cooperating molecule is IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)
Capobianchi
M R
MR
Institute of Virology, University La Sapienza, Rome, Italy.
Mattana
P
P
Mercuri
F
F
Conciatori
G
G
Ameglio
F
F
Ankel
H
H
Dianzani
F
F
D000143:Acids; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood; D002460:Cell Line; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D006031:Glycosylation; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007369:Interferon Inducers; D016898:Interferon-alpha / Q000737:chemistry* / Q000302:isolation & purification; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D012333:RNA, Messenger / Q000378:metabolism
D000143:Acids; D007369:Interferon Inducers; D016898:Interferon-alpha; D012333:RNA, Messenger; D007371:Interferon-gamma