The biological effects of five feline IFN-α subtypes

• Published in: Veterinary immunology and immunopathology Vol. 99; no. 3; pp. 153 - 167
• Main Authors: Baldwin, Susan L, Powell, Tim D, Sellins, Karen S, Radecki, Steven V, John Cohen, J, Milhausen, Michael J
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2004
• Subjects: Animals; Antiproliferation; Apoptosis; Base Sequence; Caliciviridae Infections - immunology; Caliciviridae Infections - veterinary; Caliciviridae Infections - virology; Calicivirus, Feline - immunology; Cat Diseases - immunology; Cat Diseases - virology; Cats; CHO Cells; Cricetinae; Cytopathogenic Effect, Viral - immunology; Feline calicivirus; Feline IFN-α; Female; Fibroblasts; GTP-Binding Proteins - immunology; Inhibitory Concentration 50; Interferon-alpha - classification; Interferon-alpha - genetics; Interferon-alpha - immunology; Male; Molecular Sequence Data; Myxovirus Resistance Proteins; Necrosis; Reverse Transcriptase Polymerase Chain Reaction; Rhabdoviridae Infections - immunology; Rhabdoviridae Infections - veterinary; Rhabdoviridae Infections - virology; RNA, Viral - chemistry; RNA, Viral - genetics; Sequence Analysis, DNA; Vesicular stomatitis Indiana virus - immunology; Vesicular stomatitis virus; Antiproliferation; Vesicular stomatitis virus; Feline calicivirus; Feline IFN-α; Mx; Necrosis; Apoptosis
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2004.01.012

IFN-α has been shown to induce both antiviral and antiproliferative activities in animals. This report describes the biological activity of five recently identified feline IFN-α subtypes expressed in the Chinese hamster ovary (CHO) cell line (rfeIFN-α1[CHO], rfeIFN-α2[CHO], rfeIFN-α3[CHO], rfeIFN-α5[CHO] and rfeIFN-α6[CHO]) and the feIFN-α6 subtype expressed in and purified from Pichia pastoris (rfeIFN-α6[ P. pastoris]). The rfeIFN-α[CHO] subtypes were tested for antiviral activity against either Vesicular stomatitis virus (VSV) or feline calicivirus (FCV) infected feline embryonic fibroblast cell line (AH927) or Crandell feline kidney cell line (CRFK). Antiviral activity was induced against both VSV and FCV infected AH927 cells and VSV infected CRFK cells by all five of the rfeIFN-α[CHO] subtypes and rfeIFN-α6[ P. pastoris]. In addition, the IFN-α inducible Mx gene (associated with antiviral activity) was upregulated in vivo 24 h following treatment with rfeIFN-α6[ P. pastoris], compared to baseline levels seen prior to treatment. All of the rfeIFN-α[CHO] subtypes and rfeIFN-α6[ P. pastoris] exhibited antiproliferative activity in the FeT-J cell line (an IL-2 independent feline T-cell line). Both necrosis and apoptosis were observed in rfeIFN-α6[ P. pastoris]-treated FeT-J cells. The rfeIFN-α3[CHO] subtype consistently exhibited lower antiviral and antiproliferative activity compared to that observed with the other four rfeIFN-α[CHO] subtypes. In summary, this paper demonstrates that five previously described feIFN-α subtypes induce both antiviral and antiproliferative activities in vitro and are capable of upregulating the feMx gene in vivo.