Structure/Function Studies with Interferon Tau: Evidence for Multiple Active Sites

Carol H. Pontzer, Troy L. Ott, Fuller W. Bazer, Howard M. Johnson

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

A novel interferon (IFN), called IFN-tau (IFN-τ), has recently been discovered and has been shown to be a pregnancy recognition hormone. Unlike known IFNs, however, IFN-τ exhibits high antiviral and antiproliferative activity without cytotoxicity. The structural basis for IFN-τ function has been examined using six overlapping synthetic peptides corresponding to the entire ovine (Ov) IFN-τ sequence. Four peptides representing amino acids 1–37, 62–92, 119–150, and 139–172 inhibited OvIFN-τ antiviral activity in a dose-dependent manner. Polyclonal antipeptide antisera directed against the same four peptides blocked OvIFN-τ binding and antiviral activity, confirming the specificity of the peptide competitions. Because IFN-τ and IFN-α both interact with the type I IFN receptor, peptide inhibition of bovine and human IFNα activity was also determined. Of importance, only three peptides, OvIFN-τ(62–92), (119–150), and (139–172) inhibited IFN-α antiviral activity. The amino-terminal IFN-τ peptide, OvIFN-τ(l–37), was not inhibitory. These data suggest that the internal and carboxy-terminal reactive domains of IFN-τ may interact with a common type I IFN site on the receptor, while the amino terminus interacts with a site that elicits activity unique to OvIFN-τ. Finally, the antiproliferative activity of OvIFN-τ was localized primarily to the broad carboxy-terminal region, with OvIFN-τ(119–150) being the most effective inhibitor of OvIFN-τ-induced reduction of cell proliferation. Thus, multiple domains of IFN-τ have functional significance. Furthermore, because the amino-terminus of the molecule appears to interact with the type I IFN receptor in an IFN-τ-specific manner, modified IFN-τ or IFN-τ/IFN-α chimeras may be produced with selective biological activity.

Original languageEnglish (US)
Pages (from-to)133-141
Number of pages9
JournalJournal of Interferon Research
Volume14
Issue number3
DOIs
StatePublished - Jun 1994

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

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