TY - JOUR
T1 - Acid lability is not an intrinsic property of interferon-α induced by HIV-infected cells
AU - Capobianchi, M. R.
AU - Mattana, P.
AU - Mercuri, F.
AU - Conciatori, G.
AU - Ameglio, F.
AU - Ankel, H.
AU - Dianzani, F.
PY - 1992
Y1 - 1992
N2 - Human immunodeficiency virus (HIV)-infected cells induce acid-labile interferon-α (al-IFN-α) in cultures of mononuclear cells from peripheral human blood. We have investigated the physicochemical properties of such preparations to elucidate the reasons for acid-lability of this IFN. Al-IFN- α 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-α-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-α or IFN-γ. Also, upon further purification of the unglycosylated fraction on the same antibody column, all antiviral activity remains indistinguishable from conventional IFN-α. Reconstitution experiments showed that glycosylated material excluded from the anti-IFN-α 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-α 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-α and IFN-γ suggests that the cooperating molecule is IFN-γ. The presence of IFN-γ in al-IFN-α as determined by ELISA assay, by affinity chromatography on a column containing anti-IFN-γ antibody, and by dot-blot analysis of its mRNA in the induced cells, supports our conclusion that (i) there is no acid-labile IFN- α per se, (ii) al-IFN-α is a mixture of conventional IFN-α and IFN-γ, and (iii) the apparent acid-lability of al-IFN-α is due to the synergistic antiviral effects of acid-stable IFN-α and acid-labile IFN-γ which are both present in al-IFN-α.
AB - Human immunodeficiency virus (HIV)-infected cells induce acid-labile interferon-α (al-IFN-α) in cultures of mononuclear cells from peripheral human blood. We have investigated the physicochemical properties of such preparations to elucidate the reasons for acid-lability of this IFN. Al-IFN- α 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-α-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-α or IFN-γ. Also, upon further purification of the unglycosylated fraction on the same antibody column, all antiviral activity remains indistinguishable from conventional IFN-α. Reconstitution experiments showed that glycosylated material excluded from the anti-IFN-α 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-α 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-α and IFN-γ suggests that the cooperating molecule is IFN-γ. The presence of IFN-γ in al-IFN-α as determined by ELISA assay, by affinity chromatography on a column containing anti-IFN-γ antibody, and by dot-blot analysis of its mRNA in the induced cells, supports our conclusion that (i) there is no acid-labile IFN- α per se, (ii) al-IFN-α is a mixture of conventional IFN-α and IFN-γ, and (iii) the apparent acid-lability of al-IFN-α is due to the synergistic antiviral effects of acid-stable IFN-α and acid-labile IFN-γ which are both present in al-IFN-α.
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M3 - Article
C2 - 1289411
AN - SCOPUS:0026621917
VL - 12
SP - 431
EP - 438
JO - Journal of Interferon Research
JF - Journal of Interferon Research
SN - 0197-8357
IS - 6
ER -