title: The woodchuck interferon-alpha system: Cloning, family description, and biologic activity.
abstract: Interferon-alpha (IFN-alpha) is a key element in the defense against viral infection because, in addition to a direct antiviral effect, it exhibits potent immunostimulatory activity. To investigate the function of this cytokine in the woodchuck model of chronic hepatitis B, the woodchuck IFN-alpha gene (IFNA) family was cloned and examined. The data indicate that this is a multigenic family from which 12 IFNA functional sequences and four pseudogene sequences were isolated. The overall identity of the amino acid sequence among the members of the woodchuck IFN-alpha family is 85%, and the identity with the IFN-alpha family from other species such as mice and humans is 50%. The analysis of hepatic expression of IFNA genes showed that wIFNA5a was the subtype transcribed preferentially in the woodchuck liver. The wIFNA genes transcribed in the liver were tested in an eukaryotic expression system and were found to enhance 2-5-oligoadenylate synthetase (2-5-OAS) mRNA levels and to posses a potent antiviral activity. Cloning of woodchuck IFNA genes will allow testing diverse forms of IFN-alpha delivery as well as different combination therapies in woodchuck hepatitis virus infection, thus providing useful information for the design of new strategies for the treatment of patients with chronic hepatitis B.
authors.affiliation: Division of Hepatology and Gene Therapy, University Clinic and Medical School, University of Navarra, Pamplona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Berraondo
authors.forename: Raquel
authors.initials: R
authors.lastname: García-Navarro
authors.forename: Gloria
authors.initials: G
authors.lastname: González-Aseguinolaza
authors.forename: Africa
authors.initials: A
authors.lastname: Vales
authors.forename: Begoña
authors.initials: B
authors.lastname: Blanco-Urgoiti
authors.forename: Esther
authors.initials: E
authors.lastname: Larrea
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Riezu-Boj
authors.forename: Jesús
authors.initials: J
authors.lastname: Prieto
authors.forename: Juan
authors.initials: J
authors.lastname: Ruiz
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D003001:Cloning, Molecular; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004195:Disease Models, Animal; D017919:Hepatitis B Virus, Woodchuck / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008392:Marmota; D008969:Molecular Sequence Data; D005810:Multigene Family; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D015088:2',5'-Oligoadenylate Synthetase