First detected case of rabbit Haemorrhagic disease virus 2 (RHDV2) in the Irish hare (Lepus timidus hibernicus)

Abstract Background Rabbit haemorrhagic disease virus (RHDV) is a Lagovirus, a subgroup of the family Caliciviridae. RHDV2 is a variant first described in France in 2010, and has since spread globally. It has been reported in several Lagomorph species (rabbits, hares, and their relatives) as well as other mammals including voles and shrews. The disease has raised international concerns for its potential impact on population abundance trajectories, particularly as 25% of Lagomorphs are currently Red-Listed by the International Union for the Conservation of Nature (IUCN). The Irish hare (Lepus timidus hibernicus) is a subspecies of the mountain hare, L. timidus, and is endemic to Ireland, making it an Evolutionarily Significant Unit of intrinsic value. Case presentation The first case of RHDV2 was detected in a wild Irish hare in July 2019. The individual exhibited atypical neurological behaviour (running in circles) prior to death. On necropsy, pink tinged foam was seen in the trachea and congestion was noted in the lungs, but there was no evidence of haemorrhages in any other organ. Both the liver and spleen were tested by reverse transcription real time qPCR confirming high levels of RHDV2 RNA. Histopathology confirmed multifocal necrotising hepatitis. Conclusion The Irish hare is susceptible to RHDV2 infection. Further investigation is warranted to explore the clinical, epidemiological, and population biology implications.

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The emergence of rabbit haemorrhagic disease virus: will a non-pathogenic strain protect the UK?

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2001.0897 ◽

2001 ◽

Vol 356 (1411) ◽

pp. 1087-1095 ◽

Cited By ~ 22

Author(s):

P.J. White ◽

R.A. Norman ◽

R.C. Trout ◽

E.A. Gould ◽

P.J. Hudson

Keyword(s):

Disease Virus ◽

Pathogenic Strain ◽

Rabbit Haemorrhagic Disease Virus ◽

Rabbit Haemorrhagic Disease ◽

Seroprevalence Data ◽

Age Structured ◽

Reproductive Rates ◽

The Uk ◽

Haemorrhagic Disease ◽

Age Structured Model

Rabbit haemorrhagic disease virus emerged in China in 1984, and has killed hundreds of millions of wild rabbits in Australia and Europe. In the UK there appears to be an endemic non–pathogenic strain, with high levels of seroprevalence being recorded, in the absence of associated mortality. Using a seasonal, age–structured model we examine the hypothesis that differences in rabbit population demography differentially affect the basic reproductive rates ( R 0 ) of the pathogenic and non–pathogenic strains, leading to each dominating in some populations and not others. The strain with the higher R 0 excluded the other, with the dynamics depending upon the ratio of the two R 0 values. When the non–pathogenic strain dominated, the pathogenic strain caused only transient mortality, although this could be significant when the two R 0 values were similar. When the pathogenic strain dominated, repeated epidemics led to host eradication. Seroprevalence data suggest that the non–pathogenic strain may be protecting some, but not all UK populations, with half being ‘at risk’ from invasion by the pathogenic strain and a fifth prone to significant transient mortality. We identify key questions for empirical research to test this prediction.

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Distribution of Rabbit Haemorrhagic Disease Virus RNA in Experimentally Infected Rabbits

Journal of Comparative Pathology ◽

10.1053/jcpa.2000.0440 ◽

2001 ◽

Vol 124 (2-3) ◽

pp. 134-141 ◽

Cited By ~ 19

Author(s):

T. Kimura ◽

I. Mitsui ◽

Y. Okada ◽

T. Furuya ◽

K. Ochiai ◽

...

Keyword(s):

Disease Virus ◽

Rabbit Haemorrhagic Disease Virus ◽

Virus Rna ◽

Rabbit Haemorrhagic Disease ◽

Haemorrhagic Disease

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Molecular epidemiology of Rabbit haemorrhagic disease virus

Journal of General Virology ◽

10.1099/0022-1317-83-10-2461 ◽

2002 ◽

Vol 83 (10) ◽

pp. 2461-2467 ◽

Cited By ~ 72

Author(s):

S. R. Moss ◽

S. L. Turner ◽

R. C. Trout ◽

P. J. White ◽

P. J. Hudson ◽

...

Keyword(s):

Disease Virus ◽

Nucleotide Sequencing ◽

Molecular Evidence ◽

Rabbit Haemorrhagic Disease Virus ◽

Rabbit Haemorrhagic Disease ◽

Molecular Phylogenetic ◽

Virulent Virus ◽

Rabbit Bone ◽

European Rabbits ◽

Haemorrhagic Disease

Millions of domestic and wild European rabbits (Oryctolagus cuniculus) have died in Europe, Asia, Australia and New Zealand during the past 17 years following infection by Rabbit haemorrhagic disease virus (RHDV). This highly contagious and deadly disease was first identified in China in 1984. Epidemics of RHDV then radiated across Europe until the virus apparently appeared in Britain in 1992. However, this concept of radiation of a new and virulent virus from China is not entirely consistent with serological and molecular evidence. This study shows, using RT–PCR and nucleotide sequencing of RNA obtained from the serum of healthy rabbits stored at 4 °C for nearly 50 years, that, contrary to previous opinions, RHDV circulated as an apparently avirulent virus throughout Britain more than 50 years ago and more than 30 years before the disease itself was identified. Based on molecular phylogenetic analysis of British and European RHDV sequences, it is concluded that RHDV has almost certainly circulated harmlessly in Britain and Europe for centuries rather than decades. Moreover, analysis of partial capsid sequences did not reveal significant differences between RHDV isolates that came from either healthy rabbits or animals that had died with typical haemorrhagic disease. The high stability of RHDV RNA is also demonstrated by showing that it can be amplified and sequenced from rabbit bone marrow samples collected at least 7 weeks after the animal has died.

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Immunogenicity in Rabbits of Virus-Like Particles from a Contemporary Rabbit Haemorrhagic Disease Virus Type 2 (GI.2/RHDV2/b) Isolated in The Netherlands

Viruses ◽

10.3390/v11060553 ◽

2019 ◽

Vol 11 (6) ◽

pp. 553 ◽

Cited By ~ 5

Author(s):

Qiuhong Miao ◽

Ruibing Qi ◽

Luut Veldkamp ◽

Jooske Ijzer ◽

Marja L. Kik ◽

...

Keyword(s):

The Netherlands ◽

Disease Virus ◽

Genome Sequence ◽

Insect Cells ◽

Rabbit Haemorrhagic Disease Virus ◽

Virus Like Particles ◽

Rabbit Haemorrhagic Disease ◽

Domestic Rabbits ◽

Haemorrhagic Disease

Rabbit haemorrhagic disease virus (RHDV) type 2 (GI.2/RHDV2/b) is an emerging pathogen in wild rabbits and in domestic rabbits vaccinated against RHDV (GI.1). Here we report the genome sequence of a contemporary RHDV2 isolate from the Netherlands and investigate the immunogenicity of virus-like particles (VLPs) produced in insect cells. RHDV2 RNA was isolated from the liver of a naturally infected wild rabbit and the complete viral genome sequence was assembled from sequenced RT-PCR products. Phylogenetic analysis based on the VP60 capsid gene demonstrated that the RHDV2 NL2016 isolate clustered with other contemporary RHDV2 strains. The VP60 gene was cloned in a baculovirus expression vector to produce VLPs in Sf9 insect cells. Density-gradient purified RHDV2 VLPs were visualized by transmission electron microscopy as spherical particles of around 30 nm in diameter with a morphology resembling authentic RHDV. Immunization of rabbits with RHDV2 VLPs resulted in high production of serum antibodies against VP60, and the production of cytokines (IFN-γ and IL-4) was significantly elevated in the immunized rabbits compared to the control group. The results demonstrate that the recombinant RHDV2 VLPs are highly immunogenic and may find applications in serological detection assays and might be further developed as a vaccine candidate to protect domestic rabbits against RHDV2 infection.

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Novel Trivalent Vectored Vaccine for Control of Myxomatosis and Disease Caused by Classical and a New Genotype of Rabbit Haemorrhagic Disease Virus

Vaccines ◽

10.3390/vaccines8030441 ◽

2020 ◽

Vol 8 (3) ◽

pp. 441 ◽

Cited By ~ 1

Author(s):

Sylvia Reemers ◽

Leon Peeters ◽

Joyce van Schijndel ◽

Beth Bruton ◽

David Sutton ◽

...

Keyword(s):

Disease Virus ◽

Myxoma Virus ◽

European Rabbit ◽

Viral Diseases ◽

Serological Response ◽

Rabbit Haemorrhagic Disease Virus ◽

Rabbit Haemorrhagic Disease ◽

New Genotype ◽

Vectored Vaccine ◽

Haemorrhagic Disease

Myxoma virus (MV) and rabbit haemorrhagic disease virus (RHDV) are the major causes of lethal viral diseases in the European rabbit. In 2010, a new RHDV genotype (RHDV2) emerged in the field that had limited cross-protection with the classical RHDV (RHDV1). For optimal protection of rabbits and preventing spread of disease, a vaccine providing protection against all three key viruses would be ideal. Therefore, a novel trivalent myxoma vectored RHDV vaccine (Nobivac Myxo-RHD PLUS) was developed similar to the existing bivalent myxoma vectored RHDV vaccine Nobivac Myxo-RHD. The new vaccine contains the Myxo-RHDV1 strain already included in Nobivac Myxo-RHD and a similarly produced Myxo-RHDV2 strain. This paper describes several key safety and efficacy studies conducted for European licensing purposes. Nobivac Myxo-RHD PLUS showed to be safe for use in rabbits from five weeks of age onwards, including pregnant rabbits, and did not spread from vaccinated rabbits to in-contact controls. Furthermore, protection to RHDV1 and RHDV2 was demonstrated by challenge, while the serological response to MV was similar to that after vaccination with Nobivac Myxo-RHD. Therefore, routine vaccination with Nobivac Myxo-RHD PLUS can prevent the kept rabbit population from these major viral diseases.

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The reintroduction, and subsequent impact, of rabbit haemorrhagic disease virus in a population of wild rabbits in south-western Australia

Wildlife Research ◽

10.1071/wr04025 ◽

2005 ◽

Vol 32 (2) ◽

pp. 139 ◽

Cited By ~ 11

Author(s):

John S. Bruce ◽

Laurie E. Twigg

Keyword(s):

Disease Virus ◽

Western Australia ◽

Morbidity Rate ◽

Rabbit Haemorrhagic Disease Virus ◽

Rabbit Population ◽

Rabbit Haemorrhagic Disease ◽

Deliberate Release ◽

Haemorrhagic Disease ◽

The Impact ◽

Variable Impact

The natural arrival of rabbit haemorrhagic disease virus (RHDV) in south-western Australia in September 1996 resulted in a reduction in rabbit numbers of ~65% (~90% morbidity, with ~72% mortality of infected rabbits). As no signs of the disease (clinical or serological) were seen over the next two years, and as rabbit numbers over the last 12-month monitoring period at the site were similar to those observed before the natural 1996 RHDV epizootic (i.e. pre-RHD), RHDV was deliberately reintroduced into this rabbit population in April 1999 (autumn). Seven RHDV-inoculated rabbits were released prior to the main breeding season when <3% of sampled rabbits (n = 118) were seropositive for RHDV antibodies. Following the deliberate release, the overall decline in rabbit numbers (68%) was comparable to that seen during the natural 1996 epizootic. However, on the basis of the observed changes in rabbit numbers, and in their serology, the impact of the deliberate RHDV release appeared to be more variable across the six trapping areas than was seen during the natural 1996 spring epizootic. The reductions in rabbit numbers on these areas 6–8 weeks after RHDV-release ranged from 55% to 90%. The serology of the surviving rabbits on the trapping areas was also variable over this period, with the proportion of seropositive rabbits ranging from 5% to 90%. Overall, only 15% of the surviving rabbit population showed evidence of recent challenge by RHDV, giving a morbidity rate of 73% 8 weeks after the release. However, over 90% of infected rabbits died. This provides further evidence that some rabbits remained un-challenged by RHDV for up to 8 weeks after its release. The variable impact of the April 1999 release may have been partially caused by the observed differences in abundance of insect vectors, and/or an apparent increase in the incidence of non-virulent RHDV in the months preceding the release.

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Potential use of myxoma virus and rabbit haemorrhagic disease virus to control feral rabbits in the Kerguelen Archipelago

Wildlife Research ◽

10.1071/wr03084 ◽

2004 ◽

Vol 31 (4) ◽

pp. 415 ◽

Cited By ~ 6

Author(s):

B. D. Cooke ◽

J.-L. Chapuis ◽

V. Magnet ◽

A. Lucas ◽

J. Kovaliski

Keyword(s):

Disease Virus ◽

Disease Transmission ◽

Biological Control Agent ◽

Myxoma Virus ◽

European Rabbit ◽

Rabbit Haemorrhagic Disease Virus ◽

Rabbit Haemorrhagic Disease ◽

Haemorrhagic Disease ◽

Low Prevalence ◽

Kerguelen Archipelago

Rabbits have caused enormous damage to the vegetation on seven islands in the sub-Antarctic Kerguelen archipelago, including the main island, Grande Terre. Rabbit sera collected during 2001–02 were tested for antibodies against myxoma virus and rabbit haemorrhagic disease virus with a view to considering the wider use of these viruses to control rabbits. The results confirmed work done 15–20 years earlier that suggested that myxoma virus has not spread across all parts of Grande Terre and occurs at low prevalence among rabbits. By contrast, on Ile du Cimetière, where European rabbit fleas were introduced in 1987–88, the prevalence of myxoma antibodies is high and the rabbit population is relatively low, supporting the idea that the fleas are effective vectors of myxoma virus. Consequently, there should be benefits in releasing fleas on Grand Terre to enhance disease transmission. Reactivity of some rabbit sera in RHD-specific ELISAs suggested that a virus similar to RHDV may be present at low prevalence on Grande Terre but most rabbits are likely to be susceptible and this virus could be considered for use as a future biological control agent.

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