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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.

SUBMITTER: Kerr PJ

PROVIDER: S-EPMC5349684 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.

Kerr Peter J PJ Cattadori Isabella M IM Rogers Matthew B MB Fitch Adam A Geber Adam A Liu June J Sim Derek G DG Boag Brian B Eden John-Sebastian JS Ghedin Elodie E Read Andrew F AF Holmes Edward C EC

PLoS pathogens 20170302 3

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 t ...[more]

PMID: 28253375

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Project description:To characterize the ongoing evolution of myxoma virus in Australian rabbits, we used experimental infections of laboratory rabbits to determine the virulence and disease phenotypes of recent virus isolates. The viruses, collected between 2012 and 2015, fell into three lineages, one of which, lineage c, experienced a punctuated increase in evolutionary rate. All viruses were capable of causing acute death with aspects of neutropenic septicemia, characterized by minimal signs of myxomatosis, the occurrence of pulmonary edema and bacteria invasions throughout internal organs, but with no inflammatory response. For the viruses of highest virulence all rabbits usually died at this point. In more attenuated viruses, some rabbits died acutely, while others developed an amyxomatous phenotype. Rabbits that survived for longer periods developed greatly swollen cutaneous tissues with very high virus titers. This was particularly true of lineage c viruses. Unexpectedly, we identified a line of laboratory rabbits with some innate resistance to myxomatosis and used these in direct comparisons with the fully susceptible rabbit line. Importantly, the same disease phenotype occurred in both susceptible and resistant rabbits, although virulence was shifted toward more attenuated grades in resistant animals. We propose that selection against inflammation at cutaneous sites prolongs virus replication and enhances transmission, leading to the amyxomatous phenotype. In some virus backgrounds this creates an immunosuppressive state that predisposes to high virulence and acute death. The alterations in disease pathogenesis, particularly the overwhelming bacterial invasions that characterize the modern viruses, suggest that their virulence grades are not directly comparable with earlier studies. IMPORTANCE The evolution of the myxoma virus (MYXV) following its release as a biological control for European rabbits in Australia is the textbook example of the coevolution of virus virulence and host resistance. However, most of our knowledge of MYXV evolution only covers the first few decades of its spread in Australia and often with little direct connection between how changes in virus phenotype relate to those in the underlying virus genotype. By conducting detailed experimental infections of recent isolates of MYXV in different lines of laboratory rabbits, we examined the ongoing evolution of MYXV disease phenotypes. Our results reveal a wide range of phenotypes, including an amyxomatous type, as well as the impact of invasive bacteria, that in part depended on the level of rabbit host resistance. These results provide a unique insight into the complex virus and host factors that combine to shape disease phenotype and viral evolution.

Project description:BackgroundBuying behaviours of food-allergic consumers can affect the risk they incur. An online survey was undertaken to understand the characteristics and buying behaviours of food-allergic consumers in Great Britain (GB) and people buying food for them.MethodsDescriptive study of food-allergic individuals in GB and their buying behaviours, based on a survey of 500 food-allergic consumers and 500 people buying for allergic individuals.ResultsFruit and vegetables were the most commonly mentioned food allergens for adults, cows' milk in school-age children and eggs in younger children. 45% of respondents reported a formal diagnosis, almost half (48%) by a specialist. Significantly (P < 0.0001) more respondents reporting severe symptoms were likely to be formally diagnosed, but most reactions remained unreported. Nearly 2/3 of respondents always read product labels first time, however only 1/3 on every occasion. Only a third of respondents always avoided products with 'may contain' labels. Respondents reporting severe symptoms, albeit still a minority, showed significantly (P = 0.0026) more cautious buying behaviours.ConclusionsAlthough self-reported, the pattern of food allergy reflects other studies. A minority of food-allergic individuals in GB, even among those reporting severe symptoms, have a formal diagnosis and most never come to the attention of health services, suggesting that food allergies are under-estimated while more severe reactors are over-represented in GB clinic populations. A substantial proportion of respondents regularly take risks when purchasing food including those reporting severe reactions, confirming that current application of precautionary labelling to mitigate and communicate risk is of limited effectiveness. Furthermore the failure of most food-allergic consumers to read labels on every occasion highlights the importance of thinking beyond legal compliance when designing labels, for example when adding an allergen to a product that previously did not contain it, the change should be flagged on the front of the pack to alert allergic consumers.

Dataset Information

Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.

Publications

Genomic and phenotypic characterization of myxoma virus from Great Britain reveals multiple evolutionary pathways distinct from those in Australia.

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