Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.
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.
Kerr
P J
PJ
Pest Animal Control Cooperative Research Centre, CSIRO Sustainable Ecosystems, Canberra, ACT, 2601, Australia. peter.kerr@csiro.au
Perkins
H D
HD
Inglis
B
B
Stagg
R
R
McLaughlin
E
E
Collins
S V
SV
Van Leeuwen
B H
BH
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
D015847:Interleukin-4