Myxoma virus expressing interleukin-15 fails to cause lethal myxomatosis in European rabbits.
Myxoma virus (MYXV) is a poxvirus pathogenic only for European rabbits, but its permissiveness in human cancer cells gives it potential as an oncolytic virus. A recombinant MYXV expressing both the tdTomato red fluorescent protein and interleukin-15 (IL-15) (vMyx-IL-15-tdTr) was constructed. Cells infected with vMyx-IL-15-tdTr secreted bioactive IL-15 and had in vitro replication kinetics similar to that of wild-type MYXV. To determine the safety of this virus for future oncolytic studies, we tested its pathogenesis in European rabbits. In vivo, vMyx-IL-15-tdTr no longer causes lethal myxomatosis. Thus, ectopic IL-15 functions as an antiviral cytokine in vivo, and vMyx-IL-15-tdTr is a safe candidate for animal studies of oncolytic virotherapy.
Liu
Jia
J
Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
Wennier
Sonia
S
Reinhard
Mary
M
Roy
Edward
E
MacNeill
Amy
A
McFadden
Grant
G
D000818:Animals; D005822:Genetic Vectors / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D009233:Myxoma virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D009234:Myxomatosis, Infectious / Q000473:pathology*; D010957:Plasmids / Q000235:genetics; D011817:Rabbits; D015996:Survival Rate; D014779:Virus Replication
D019409:Interleukin-15