The cross-species antiviral activities of different IFN-tau subtypes on bovine, murine, and human cells: contradictory evidence for therapeutic potential.
It is claimed that interferon-tau (IFN-tau) has broad cross-species reactivity and less cytotoxicity than other type I IFN when used at high concentration either in vitro or in living animals. It can also amelioriate the development of experimental allergic encephalomyelitis (EAE) without the usual side effects of IFN therapy in mice autoimmunized with myelin basic protein. For these reasons, IFN-tau may have therapeutic potential in humans. Here, the antiviral (AV) activities of eight different recombinant IFN-tau were compared with those of several bovine, human, and murine type I IFN on bovine MDBK cells, murine L929 cells, and human WISH cells. The data show that only one of the IFN-tau, OvIFN-tau4, has broad cross-species reactivity. It was comparable in this respect to HuIFN-omega1 and HuIFN-alpha1. The other IFN-tau, including the variant form (OvIFN-tau1mod) tested by others in cytotoxicity experiments and for its ability to protect mice against EAE, had relatively weak AV activity on mouse and human cells. It is possibly because this particular bioengineered form of IFN-tau binds the common type I receptor of these two species with such low affinity that it lacks cytotoxic effects. The basis for its potent anti-EAE activity is unclear, but it seems possible that it does not involve the type I IFN receptor.
Alexenko
A P
AP
Department of Animal Sciences, University of Missouri, Columbia 65211, USA.
Ealy
A D
AD
Roberts
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control; D006801:Humans; D007370:Interferon Type I / Q000145:classification / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D011257:Pregnancy Proteins / Q000145:classification / Q000235:genetics / Q000494:pharmacology*; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D000998:Antiviral Agents; D007370:Interferon Type I; D011257:Pregnancy Proteins; D017471:Receptors, Interferon; D011994:Recombinant Proteins; C020947:interferon tau