title: Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.
abstract: Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization.
authors.affiliation: Pest Animal Control Cooperative Research Centre, CSIRO Sustainable Ecosystems, Canberra, ACT, 2601, Australia. peter.kerr@csiro.au
authors.forename: P J
authors.initials: PJ
authors.lastname: Kerr
authors.forename: H D
authors.initials: HD
authors.lastname: Perkins
authors.forename: B
authors.initials: B
authors.lastname: Inglis
authors.forename: R
authors.initials: R
authors.lastname: Stagg
authors.forename: E
authors.initials: E
authors.lastname: McLaughlin
authors.forename: S V
authors.initials: SV
authors.lastname: Collins
authors.forename: B H
authors.initials: BH
authors.lastname: Van Leeuwen
mesh_terms: D000818:Animals; D002460:Cell Line; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D009233:Myxoma virus / Q000235:genetics* / Q000472:pathogenicity; D009234:Myxomatosis, Infectious / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D014774:Virulence
chemical_list: D015847:Interleukin-4