Myxoma Virus Expressing Interleukin-15 Fails To Cause Lethal Myxomatosis in European Rabbits

Abstract

Myxoma virus (MYXV) is a poxvirus pathogenic only for

Intraventricular injection of myxoma virus results in transient expression of viral protein in mouse brain ependymal and subventricular cells

“…MYXV-Red is a recombinant myxoma virus derived from the Lausanne strain that expresses tdTomato red protein under the control of a synthetic vaccinia virus early/late promoter, and was originally designated vMyx-tdTr (Liu et al, 2009). In studies involving intracranial injections of MYXV-Red to evaluate the therapeutic effect on brain tumours, we noticed occasional red ependymal cells when the needle track passed near the lateral ventricle (Fig.…”

Myxoma Virus M064 Is a Novel Member of the Poxvirus C7L Superfamily of Host Range Factors That Controls the Kinetics of Myxomatosis in European Rabbits

“…Except for the 5= 83 bp and the 3= 86 bp of M064R, the central region of the gene (about 82%) was deleted and replaced by an enhanced green fluorescent protein (EGFP) expression cassette driven by a poxvirus early/late synthetic promoter (8). The recombination and purification procedures were conducted as previously described (7,8). First, the growth of the knockout virus was evaluated in vitro by one-step or multiple-step growth curves, as previously reported (7,8), in various different indicator cell lines and compared with that of the wild-type (wt) MYXV (vMyxGFP).…”

“…The recombination and purification procedures were conducted as previously described (7,8). First, the growth of the knockout virus was evaluated in vitro by one-step or multiple-step growth curves, as previously reported (7,8), in various different indicator cell lines and compared with that of the wild-type (wt) MYXV (vMyxGFP). In many of these cell lines, both the M063 and M062 knockout viruses manifested dramatic and severe replication defects (2,8).…”

“…Four groups of European rabbits that had been treated with vehicle (phosphate-buffered saline [PBS] only) (n ϭ 2), 1,000 focus-forming units (FFU) of wt MYXV Lausanne strain (vMyx-Lau) (n ϭ 2), vMyxM064-KO (n ϭ 4), and the revertant virus (vMyxM064-Rev) (n ϭ 3) were inoculated intradermally with the corresponding reagent in a 100-l volume of vehicle. A clinical scoring system that has been described in detail previously (7,8) was used for daily evaluation of the progression of myxomatosis in these animals. The average daily score from each group was plotted and used as a measure of disease progression.…”

Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity

“…16 As well, the treatment of established tumors with IL-15 improves survival 17 and pre-association of IL-15 to its receptor a chain further enhances NK and CD8 T-cell activation, proliferation 18,19 and anti-tumour activity. Finally, human (h)IL-15 has also been added to immunotherapeutic 20 and oncolytic vectors 21 in hopes of improving their therapeutic efficacy.…”