Genetic Variability of Myxoma Virus Genomes

Myxomatosis is a recurrent problem on rabbit farms throughout Europe despite the success of vaccines. To identify gene variations of field and vaccine strains that may be responsible for changes in virulence, immunomodulation, and immunoprotection, the genomes of 6 Myxoma virus strains (MYXV) were sequenced: German field isolates Munich-1, FLI-H, 2604, 3207, vaccine strain MAV, and challenge strain ZA. The analyzed genomes ranged from 147.6 kb (strain MAV) to 161.8 kb (strain 3207) in size. All sequences were affected by several mutations, covering 24-93 open reading frames (ORFs) and resulted in amino acid (aa) substitutions, insertions, or deletions. Only strains Munich-1 and MAV revealed the deletion of 10 (M007L-M015L) and 11 (M007L-M008.1L, M149R-M008.1R) ORFs, respectively. Major differences were observed in the 27 immunomodulatory proteins encoded by MYXV. Compared to the reference strain Lausanne, strains FLI-H, 2604, 3207, and ZA showed the highest aa identity (>98.4%). In strains Munich-1 and MAV the deletion of 5 and 10 ORFs, respectively, was observed, encoding immunomodulatory proteins with ankyrin repeats or members of the family of serine protease inhibitors. Furthermore, putative immunodominant surface proteins with homology to vaccinia virus (VACV) were investigated in the sequenced strains. Only strain MAV revealed aa substitutions and frameshift mutations above average. Finally, we performed recombination analysis and found signs of recombination in vaccine strain MAV. Phylogenetic analysis showed a close relationship of strain MAV and the MSW strain of Californian MYXV. However, in a challenge model strain MAV provided full protection against lethal challenges with strain ZA.