title: Benign Rabbit Caliciviruses Exhibit Evolutionary Dynamics Similar to Those of Their Virulent Relatives.
abstract: Two closely related caliciviruses cocirculate in Australia: rabbit hemorrhagic disease virus (RHDV) and rabbit calicivirus Australia 1 (RCV-A1). RCV-A1 causes benign enteric infections in the European rabbit (Oryctolagus cuniculus) in Australia and New Zealand, while its close relative RHDV causes a highly pathogenic infection of the liver in the same host. The comparison of these viruses provides important information on the nature and trajectory of virulence evolution, particularly as highly virulent strains of RHDV may have evolved from nonpathogenic ancestors such as RCV-A1. To determine the evolution of RCV-A1 we sequenced the full-length genomes of 44 RCV-A1 samples isolated from healthy rabbits and compared key evolutionary parameters to those of its virulent relative, RHDV. Despite their marked differences in pathogenicity and tissue tropism, RCV-A1 and RHDV have evolved in a very similar manner. Both viruses have evolved at broadly similar rates, suggesting that their dynamics are largely shaped by high background mutation rates, and both exhibit occasional recombination and an evolutionary environment dominated by purifying selection. In addition, our comparative analysis revealed that there have been multiple changes in both virulence and tissue tropism in the evolutionary history of these and related viruses. Finally, these new genomic data suggest that either RCV-A1 was introduced into Australia after the introduction of myxoma virus as a biocontrol agent in 1950 or there was drastic reduction of the rabbit population, and hence of RCV-A1 genetic diversity, perhaps coincident with the emergence of myxoma virus.
  
  
  
  The comparison of closely related viruses that differ profoundly in propensity to cause disease in their hosts offers a powerful opportunity to reveal the causes of changes in virulence and to study how such changes alter the evolutionary dynamics of these pathogens. Here we describe such a novel comparison involving two closely related RNA viruses that cocirculate in Australia, the highly virulent rabbit hemorrhagic disease virus (RHDV) and the nonpathogenic rabbit calicivirus Australia 1 (RCV-A1). Both viruses infect the European rabbit, but they differ in virulence, tissue tropism, and mechanisms of transmission. Surprisingly, and despite these fundamental differences, RCV-A1 and RHDV have evolved at very similar (high) rates and with strong purifying selection. Furthermore, candidate key mutations were identified that may play a role in virulence and/or tissue tropism and therefore warrant further investigation.
authors: Marie Bashir Institute for Infectious Disease and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia Commonwealth Scientific and Industrial Research Organization, Health and Biosecurity, Black Mountain, ACT, Australia.
authors: Jackie E
authors: JE
authors: Mahar
authors: Wildlife Ecology and Management Group, Landcare Research, Lincoln, New Zealand Department of Microbiology & Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors: Leila
authors: L
authors: Nicholson
authors: Marie Bashir Institute for Infectious Disease and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
authors: John-Sebastian
authors: JS
authors: Eden
authors: Marie Bashir Institute for Infectious Disease and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
authors: Sebastián
authors: S
authors: Duchêne
authors: Marie Bashir Institute for Infectious Disease and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia Commonwealth Scientific and Industrial Research Organization, Health and Biosecurity, Black Mountain, ACT, Australia.
authors: Peter J
authors: PJ
authors: Kerr
authors: Wildlife Ecology and Management Group, Landcare Research, Lincoln, New Zealand Invasive Animals Cooperative Research Centre, University of Canberra, Bruce, ACT, Australia.
authors: Janine
authors: J
authors: Duckworth
authors: Department of Microbiology & Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors: Vernon K
authors: VK
authors: Ward
authors: Marie Bashir Institute for Infectious Disease and Biosecurity, School of Life and Environmental Sciences and Sydney Medical School, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
authors: Edward C
authors: EC
authors: Holmes
authors: Commonwealth Scientific and Industrial Research Organization, Health and Biosecurity, Black Mountain, ACT, Australia Invasive Animals Cooperative Research Centre, University of Canberra, Bruce, ACT, Australia tanja.strive@csiro.au.
authors: Tanja
authors: T
authors: Strive
mesh_terms: D000818:Animals; D001315:Australia; D005075:Biological Evolution; D002139:Caliciviridae / Q000235:genetics*; D017250:Caliciviridae Infections / Q000821:virology; D017929:Hemorrhagic Disease Virus, Rabbit / Q000235:genetics*; D008099:Liver / Q000821:virology; D009520:New Zealand; D010802:Phylogeny; D011817:Rabbits; D014774:Virulence / Q000235:genetics*