Structure/function studies with interferon tau: evidence for multiple active sites.
A novel interferon (IFN), called IFN-tau (IFN-tau), has recently been discovered and has been shown to be a pregnancy recognition hormone. Unlike known IFNs, however, IFN-tau exhibits high antiviral and antiproliferative activity without cytotoxicity. The structural basis for IFN-tau function has been examined using six overlapping synthetic peptides corresponding to the entire ovine (Ov) IFN-tau sequence. Four peptides representing amino acids 1-37, 62-92, 119-150, and 139-172 inhibited OvIFN-tau antiviral activity in a dose-dependent manner. Polyclonal antipeptide antisera directed against the same four peptides blocked OvIFN-tau binding and antiviral activity, confirming the specificity of the peptide competitions. Because IFN-tau and IFN-alpha both interact with the type I IFN receptor, peptide inhibition of bovine and human IFN alpha activity was also determined. Of importance, only three peptides, OvIFN-tau (62-92), (119-150), and (139-172) inhibited IFN-alpha antiviral activity. The amino-terminal IFN-tau peptide, OvIFN-tau(1-37), was not inhibitory. These data suggest that the internal and carboxy-terminal reactive domains of IFN-tau 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-tau. Finally, the antiproliferative activity of OvIFN-tau was localized primarily to the broad carboxy-terminal region, with OvIFN-tau(119-150) being the most effective inhibitor of OvIFN-tau-induced reduction of cell proliferation. Thus, multiple domains of IFN-tau have functional significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Pontzer
C H
CH
Department of Microbiology, University of Maryland, College Park 20742.
Ott
T L
TL
Bazer
F W
FW
Johnson
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007370:Interferon Type I / Q000737:chemistry* / Q000494:pharmacology; D008969:Molecular Sequence Data; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000737:chemistry* / Q000494:pharmacology; D011270:Pregnancy, Animal / Q000378:metabolism*; D012756:Sheep; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D007370:Interferon Type I; D011257:Pregnancy Proteins; C020947:interferon tau