scholarly journals Towards a unique and transmissible vaccine against myxomatosis and rabbit haemorrhagic disease for rabbit populations

2007 ◽  
Vol 34 (7) ◽  
pp. 567 ◽  
Author(s):  
Elena Angulo ◽  
Juan Bárcena
Keyword(s):  
Recombinant Virus ◽  
Horizontal Transmission ◽  
Myxoma Virus ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Hemorrhagic Disease ◽  
Wild Rabbit ◽  
The European Union ◽  
Vaccine Strategy ◽  
Rabbit Hemorrhagic Disease ◽  
Rabbit Haemorrhagic Disease

Currently available vaccines against myxomatosis and rabbit hemorrhagic disease virus (RHDV) are not suited to immunise wild rabbit populations, as vaccines need to be delivered individually by conventional veterinary practices. As an alternative approach, research in Spain has focused on the development of a transmissible vaccine. A recombinant virus has been constructed based on a naturally attenuated myxoma virus (MV) field strain, expressing the RHDV capsid protein (VP60). Following inoculation of rabbits, the recombinant virus (MV-VP60) induced specific antibody responses against MV and RHDV, conferring protection against lethal challenges with both viruses. Furthermore, the recombinant MV-VP60 virus showed a limited horizontal transmission capacity, either by direct contact or in a flea-mediated process, promoting immunisation of contact uninoculated animals. Efficacy and safety of the vaccine have been extensively evaluated under laboratory conditions and in a limited field trial. The development of the transmissible vaccine strategy and the steps being taken to obtain the marketing authorisation for the vaccine in the European Union are presented in this review.

scholarly journals Punctuated evolution of myxoma virus: rapid and disjunct evolution of a recent viral lineage in Australia

2018 ◽  
Author(s):  
Peter J. Kerr ◽  
John-Sebastian Eden ◽  
Francesca Di Giallonardo ◽  
David Peacock ◽  
June Liu ◽  
...  
Keyword(s):  
Myxoma Virus ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Hemorrhagic Disease ◽  
Partial Recovery ◽  
Wild Rabbit ◽  
Genome Sequences ◽  
Selection Pressures ◽  
Rabbit Hemorrhagic Disease ◽  
Evolutionary Event ◽  
European Rabbits

ABSTRACTMyxoma virus (MYXV) has been evolving in a novel host species – European rabbits – in Australia since 1950. Previous studies of viruses sampled from 1950 to 1999 revealed a remarkably clock-like evolutionary process across all Australian lineages of MYXV. Through an analysis of 49 newly generated MYXV genome sequences isolated in Australia between 2008 and 2017 we show that MYXV evolution in Australia can be characterized by three lineages, one of which exhibited a greatly elevated rate of evolutionary change and a dramatic break-down of temporal structure. Phylogenetic analysis revealed that this apparently punctuated evolutionary event occurred between 1996 and 2012. The branch leading to the rapidly evolving lineage contained a relatively high number of non-synonymous substitutions, and viruses in this lineage reversed a mutation found in the progenitor standard laboratory strain (SLS) and all previous sequences that disrupts the reading frame of theM005L/Rgene. Analysis of genes encoding proteins involved in DNA synthesis or RNA transcription did not reveal any mutations likely to cause rapid evolution. Although there was some evidence for recombination across the MYXV phylogeny, this was not associated with the increase in evolutionary rate. The period from 1996 to 2012 saw significant declines in wild rabbit numbers, due to the introduction of rabbit hemorrhagic disease and prolonged drought in south-eastern Australia, followed by the partial recovery of populations. We therefore suggest that a rapidly changing environment for virus transmission changed the selection pressures faced by MYXV and altered the course of virus evolution.IMPORTANCEThe co-evolution of myxoma virus (MYXV) and European rabbits in Australia is one of the most important natural ‘experiments’ in evolutionary biology, providing insights into virus adaptation to new hosts and the evolution of virulence. Previous studies of MYXV evolution have also shown that the virus evolves both relatively rapidly and in a strongly clock-like manner. Using newly acquired MYXV genome sequences from Australia we show that the virus has experienced a dramatic change in evolutionary behavior over the last 20 years, with a break-down in clock-like structure, the appearance of a rapidly evolving virus lineage, and the accumulation of multiple non-synonymous and indel mutations. We suggest that this punctuated evolutionary event likely reflects a change in selection pressures as rabbit numbers declined following the introduction of rabbit hemorrhagic disease virus and drought in the geographic regions inhabited by rabbits.

scholarly journals Horizontal Transmissible Protection against Myxomatosis and Rabbit Hemorrhagic Disease by Using a Recombinant Myxoma Virus

2000 ◽  
Vol 74 (3) ◽  
pp. 1114-1123 ◽  
Author(s):  
Juan Bárcena ◽  
Mónica Morales ◽  
Belén Vázquez ◽  
José A. Boga ◽  
Francisco Parra ◽  
...  
Keyword(s):  
Horizontal Transmission ◽  
Myxoma Virus ◽  
Transmissible Gastroenteritis Virus ◽  
Hemorrhagic Disease ◽  
Wild Rabbit ◽  
Rabbit Hemorrhagic Disease ◽  
Recombinant Viruses ◽  
New Strategy ◽  
Transmissible Gastroenteritis ◽  
Capsid Protein Vp60

ABSTRACT We have developed a new strategy for immunization of wild rabbit populations against myxomatosis and rabbit hemorrhagic disease (RHD) that uses recombinant viruses based on a naturally attenuated field strain of myxoma virus (MV). The recombinant viruses expressed the RHDV major capsid protein (VP60) including a linear epitope tag from the transmissible gastroenteritis virus (TGEV) nucleoprotein. Following inoculation, the recombinant viruses induced specific antibody responses against MV, RHDV, and the TGEV tag. Immunization of wild rabbits by the subcutaneous and oral routes conferred protection against virulent RHDV and MV challenges. The recombinant viruses showed a limited horizontal transmission capacity, either by direct contact or in a flea-mediated process, promoting immunization of contact uninoculated animals.

scholarly journals Punctuated Evolution of Myxoma Virus: Rapid and Disjunct Evolution of a Recent Viral Lineage in Australia

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Peter J. Kerr ◽  
John-Sebastian Eden ◽  
Francesca Di Giallonardo ◽  
David Peacock ◽  
June Liu ◽  
...  
Keyword(s):  
Myxoma Virus ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Hemorrhagic Disease ◽  
Partial Recovery ◽  
Wild Rabbit ◽  
Genome Sequences ◽  
Selection Pressures ◽  
Rabbit Hemorrhagic Disease ◽  
Evolutionary Event ◽  
European Rabbits

ABSTRACTMyxoma virus (MYXV) has been evolving in a novel host species—European rabbits—in Australia since 1950. Previous studies of viruses sampled from 1950 to 1999 revealed a remarkably clock-like evolutionary process across all Australian lineages of MYXV. Through an analysis of 49 newly generated MYXV genome sequences isolated in Australia between 2008 and 2017, we show that MYXV evolution in Australia can be characterized by three lineages, one of which exhibited a greatly elevated rate of evolutionary change and a dramatic breakdown of temporal structure. Phylogenetic analysis revealed that this apparently punctuated evolutionary event occurred between 1996 and 2012. The branch leading to the rapidly evolving lineage contained a relatively high number of nonsynonymous substitutions, and viruses in this lineage reversed a mutation found in the progenitor standard laboratory strain (SLS) and all previous sequences that disrupts the reading frame of theM005L/Rgene. Analysis of genes encoding proteins involved in DNA synthesis or RNA transcription did not reveal any mutations likely to cause rapid evolution. Although there was some evidence for recombination across the MYXV phylogeny, this was not associated with the increase in the evolutionary rate. The period from 1996 to 2012 saw significant declines in wild rabbit numbers, due to the introduction of rabbit hemorrhagic disease and prolonged drought in southeastern Australia, followed by the partial recovery of populations. It is therefore possible that a rapidly changing environment for virus transmission changed the selection pressures faced by MYXV, altering the course and pace of virus evolution.IMPORTANCEThe coevolution of myxoma virus (MYXV) and European rabbits in Australia is one of the most important natural experiments in evolutionary biology, providing insights into virus adaptation to new hosts and the evolution of virulence. Previous studies of MYXV evolution have also shown that the virus evolves both relatively rapidly and in a strongly clock-like manner. Using newly acquired MYXV genome sequences from Australia, we show that the virus has experienced a dramatic change in evolutionary behavior over the last 20 years, with a breakdown in clock-like structure, the appearance of a rapidly evolving virus lineage, and the accumulation of multiple nonsynonymous and indel mutations. We suggest that this punctuated evolutionary event may reflect a change in selection pressures as rabbit numbers declined following the introduction of rabbit hemorrhagic disease virus and drought in the geographic regions inhabited by rabbits.

scholarly journals Rabbit Hemorrhagic Disease Virus 2 (RHDV2; GI.2) Is Replacing Endemic Strains of RHDV in the Australian Landscape within 18 Months of Its Arrival

2017 ◽  
Vol 92 (2) ◽  
Author(s):  
Jackie E. Mahar ◽  
Robyn N. Hall ◽  
David Peacock ◽  
John Kovaliski ◽  
Melissa Piper ◽  
...  
Keyword(s):  
Disease Virus ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Effective Vaccine ◽  
Hemorrhagic Disease ◽  
Wild Rabbit ◽  
New Host ◽  
Content Type ◽  
Rabbit Hemorrhagic Disease ◽  
Initial Description ◽  
Ongoing Surveillance

ABSTRACTRabbit hemorrhagic disease virus 2(RHDV2;LagovirusGI.2) is a pathogenic calicivirus that affects European rabbits (Oryctolagus cuniculus) and various hare (Lepus) species. GI.2 was first detected in France in 2010 and subsequently caused epidemics in wild and domestic lagomorph populations throughout Europe. In May 2015, GI.2 was detected in Australia. Within 18 months of its initial detection, GI.2 had spread to all Australian states and territories and rapidly became the dominant circulating strain, replacingRabbit hemorrhagic disease virus(RHDV/GI.1) in mainland Australia. Reconstruction of the evolutionary history of 127 Australian GI.2 isolates revealed that the virus arrived in Australia at least several months before its initial description and likely circulated unnoticed in wild rabbit populations in the east of the continent prior to its detection. GI.2 sequences isolated from five hares clustered with sequences from sympatric rabbit populations sampled contemporaneously, indicating multiple spillover events into hares rather than an adaptation of the Australian GI.2 to a new host. Since the presence of GI.2 in Australia may have wide-ranging consequences for rabbit biocontrol, particularly with the release of the novel biocontrol agent GI.1a/RHDVa-K5 in March 2017, ongoing surveillance is critical to understanding the interactions of the various lagoviruses in Australia and their impact on host populations.IMPORTANCEThis study describes the spread and distribution ofRabbit hemorrhagic disease virus 2(GI.2) in Australia since its first detection in May 2015. Within the first 18 months following its detection, RHDV2 spread from east to west across the continent and became the dominant strain in all mainland states of Australia. This has important implications for pest animal management and for owners of pet and farmed rabbits, as there currently is no effective vaccine available in Australia for GI.2. The closely related RHDV (GI.1) is used to control overabundant wild rabbits, a serious environmental and agricultural pest in this country, and it is currently unclear how the widespread circulation of GI.2 will impact ongoing targeted wild rabbit management operations.

Sequence and genomic organization of a rabbit hemorrhagic disease virus isolated from a wild rabbit

Virus Genes ◽  
1995 ◽  
Vol 9 (2) ◽  
pp. 121-132 ◽  
Author(s):  
Denis Rasschaert ◽  
Stephanie Huguet ◽  
Marie-Francoise Madelaine ◽  
Jean-Francois Vautherot
Keyword(s):  
Disease Virus ◽  
Genomic Organization ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Hemorrhagic Disease ◽  
Wild Rabbit ◽  
Rabbit Hemorrhagic Disease

scholarly journals Evolution and Phylogeography of the Nonpathogenic Calicivirus RCV-A1 in Wild Rabbits in Australia

2010 ◽  
Vol 84 (23) ◽  
pp. 12397-12404 ◽  
Author(s):  
Marlene Jahnke ◽  
Edward C. Holmes ◽  
Peter J. Kerr ◽  
John D. Wright ◽  
Tanja Strive
Keyword(s):  
Myxoma Virus ◽  
European Rabbit ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Recent Common Ancestor ◽  
Hemorrhagic Disease ◽  
Evolutionary Analysis ◽  
Wild Rabbit ◽  
Most Recent Common Ancestor ◽  
Capsid Sequence ◽  
Australian Continent

ABSTRACT Despite its potential importance for the biological control of European rabbits, relatively little is known about the evolution and molecular epidemiology of rabbit calicivirus Australia 1 (RCV-A1). To address this issue we undertook an extensive evolutionary analysis of 36 RCV-A1 samples collected from wild rabbit populations in southeast Australia between 2007 and 2009. Based on phylogenetic analysis of the entire capsid sequence, six clades of RCV-A1 were defined, each exhibiting strong population subdivision. Strikingly, our estimates of the time to the most recent common ancestor of RCV-A1 coincide with the introduction of rabbits to Australia in the mid-19th century. Subsequent divergence events visible in the RCV-A1 phylogenies likely reflect key moments in the history of the European rabbit in Australia, most notably the bottlenecks in rabbit populations induced by the two viral biocontrol agents used on the Australian continent, myxoma virus and rabbit hemorrhagic disease virus (RHDV). RCV-A1 strains therefore exhibit strong phylogeographic separation and may constitute a useful tool to study recent host population dynamics and migration patterns, which in turn could be used to monitor rabbit control in Australia.

scholarly journals Benign Rabbit Caliciviruses Exhibit Evolutionary Dynamics Similar to Those of Their Virulent Relatives

2016 ◽  
Vol 90 (20) ◽  
pp. 9317-9329 ◽  
Author(s):  
Jackie E. Mahar ◽  
Leila Nicholson ◽  
John-Sebastian Eden ◽  
Sebastián Duchêne ◽  
Peter J. Kerr ◽  
...  
Keyword(s):  
Disease Virus ◽  
Evolutionary Dynamics ◽  
Purifying Selection ◽  
Myxoma Virus ◽  
European Rabbit ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Tissue Tropism ◽  
Hemorrhagic Disease ◽  
Rabbit Hemorrhagic Disease ◽  
Highly Virulent

ABSTRACTTwo 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.IMPORTANCEThe 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.

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