title: Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.
abstract: The co-evolution of myxoma virus (MYXV) and the European rabbit occurred independently in Australia and Europe from different progenitor viruses. Although this is the canonical study of the evolution of virulence, whether the genomic and phenotypic outcomes of MYXV evolution in Europe mirror those observed in Australia is unknown. We addressed this question using viruses isolated in the United Kingdom early in the MYXV epizootic (1954-1955) and between 2008-2013. The later UK viruses fell into three distinct lineages indicative of a long period of separation and independent evolution. Although rates of evolutionary change were almost identical to those previously described for MYXV in Australia and strongly clock-like, genome evolution in the UK and Australia showed little convergence. The phenotypes of eight UK viruses from three lineages were characterized in laboratory rabbits and compared to the progenitor (release) Lausanne strain. Inferred virulence ranged from highly virulent (grade 1) to highly attenuated (grade 5). Two broad disease types were seen: cutaneous nodular myxomatosis characterized by multiple raised secondary cutaneous lesions, or an amyxomatous phenotype with few or no secondary lesions. A novel clinical outcome was acute death with pulmonary oedema and haemorrhage, often associated with bacteria in many tissues but an absence of inflammatory cells. Notably, reading frame disruptions in genes defined as essential for virulence in the progenitor Lausanne strain were compatible with the acquisition of high virulence. Combined, these data support a model of ongoing host-pathogen co-evolution in which multiple genetic pathways can produce successful outcomes in the field that involve both different virulence grades and disease phenotypes, with alterations in tissue tropism and disease mechanisms.
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.|CSIRO Health and Biosecurity, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kerr
authors.affiliation: Center for Infectious Disease Dynamics and Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, United States of America.
authors.forename: Isabella M
authors.initials: IM
authors.lastname: Cattadori
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, United States of America.
authors.forename: Matthew B
authors.identifier: 0000-0002-4958-8971
authors.initials: MB
authors.lastname: Rogers
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, United States of America.
authors.forename: Adam
authors.initials: A
authors.lastname: Fitch
authors.affiliation: Center for Genomics & Systems Biology, Department of Biology, New York University, New York, New York 10003, United States of America.
authors.forename: Adam
authors.initials: A
authors.lastname: Geber
authors.affiliation: CSIRO Health and Biosecurity, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: June
authors.initials: J
authors.lastname: Liu
authors.affiliation: Center for Infectious Disease Dynamics and Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, United States of America.
authors.forename: Derek G
authors.initials: DG
authors.lastname: Sim
authors.affiliation: The James Hutton Institute, Invergowrie, DD2 5DA, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: Boag
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: John-Sebastian
authors.identifier: 0000-0003-1374-3551
authors.initials: JS
authors.lastname: Eden
authors.affiliation: Center for Genomics & Systems Biology, Department of Biology, New York University, New York, New York 10003, United States of America.
authors.forename: Elodie
authors.initials: E
authors.lastname: Ghedin
authors.affiliation: Center for Infectious Disease Dynamics and Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, United States of America.|Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania 16802, United States of America.
authors.forename: Andrew F
authors.identifier: 0000-0001-7604-7903
authors.initials: AF
authors.lastname: Read
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Edward C
authors.identifier: 0000-0001-9596-3552
authors.initials: EC
authors.lastname: Holmes
mesh_terms: D000818:Animals; D001315:Australia; D019143:Evolution, Molecular; D005814:Genes, Viral / Q000235:genetics; D005838:Genotype; D009233:Myxoma virus / Q000235:genetics* / Q000472:pathogenicity*; D009234:Myxomatosis, Infectious / Q000235:genetics*; D010641:Phenotype; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011817:Rabbits; D006113:United Kingdom; D014774:Virulence / Q000235:genetics*