Acid lability is not an intrinsic property of interferon-α induced by HIV-infected cells

M. R. Capobianchi, P. Mattana, F. Mercuri, G. Conciatori, F. Ameglio, H. Ankel, F. Dianzani

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)431-438
Number of pages8
JournalJournal of Interferon Research
Volume12
Issue number6
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Immunology
  • Virology

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