title: Innate immunomodulation with recombinant interferon-alpha enhances resistance of rainbow trout (Oncorhynchus mykiss) to infectious hematopoietic necrosis virus.
abstract: We examined the in vivo immunostimulatory effects of a recombinant Atlantic salmon (Salmo salar) interferon-alpha2 (rSasaIFN-alpha2). The mature rSasaIFN-alpha2, expressed and purified from Escherichia coli, was administered to rainbow trout (Oncorhynchus mykiss) via the oral, immersion, or intraperitoneal (IP) injection route. Injection of rSasaIFN-alpha2 at 0.1microg/g fish gave significantly greater protection than a phosphate buffered saline (PBS) injection against a lethal challenge of infectious hematopoietic necrosis virus (IHNV), with a relative percent survival of 39%. Relative percent survival (RPS) increased significantly to 92% when the fish were injected with rSasaIFN-alpha2 at 1microg/g fish. Antiviral protection was evident for up to 7 days post-injection of rSasaIFN-alpha2. Administration of rSasaIFN-alpha2 by the oral or immersion route was not protective, and the fish succumbed to virus infection. The level of systemic IFN-induced expression of the Mx1 gene was significantly greater (p<0.01) in the IFN-injected group than in the PBS-injected group, and this was correlated with the fish survival rates in the challenge study. We used relative quantitative real-time polymerase chain reactions to examine the systemic expression of several other IFN-induced genes (including genes for IFN1, IFN regulatory factors 1 and 2, MHC-I, STAT1, vig-1, and GBP) and found that their expression was significantly increased 1-day post-rSasaIFN-alpha2 injection. Expression of the IFN-gamma and interleukin-1beta genes was not significantly increased. Thus, a salmonid rIFN-alpha can modulate the innate immune response of rainbow trout and mediate early antiviral protection against IHNV.
authors.affiliation: Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Shirokanedai 4-6-1, Minato, Tokyo 108-8639, Japan.
authors.forename: Ei Lin
authors.initials: EL
authors.lastname: Ooi
authors.forename: Noel
authors.initials: N
authors.lastname: Verjan
authors.forename: Ikumi
authors.initials: I
authors.lastname: Haraguchi
authors.forename: Takeo
authors.initials: T
authors.lastname: Oshima
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Kondo
authors.forename: Ikuo
authors.initials: I
authors.lastname: Hirono
authors.forename: Takashi
authors.initials: T
authors.lastname: Aoki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yuki
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D029142:Infectious hematopoietic necrosis virus / Q000276:immunology*; D007370:Interferon Type I / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D017686:Oncorhynchus mykiss / Q000276:immunology* / Q000821:virology*; D011994:Recombinant Proteins; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D015996:Survival Rate
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins