scholarly journals Full-genome sequencing of German rabbit haemorrhagic disease virus uncovers recombination between RHDV (GI.2) and EBHSV (GII.1)

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Kevin P Szillat ◽  
Dirk Höper ◽  
Martin Beer ◽  
Patricia König
Keyword(s):  
Genetic Variability ◽  
Disease Virus ◽  
Full Genome ◽  
Rabbit Haemorrhagic Disease Virus ◽  
Structural Genes ◽  
Full Genome Sequencing ◽  
European Brown Hare ◽  
Whole Genome Analysis ◽  
Rabbit Haemorrhagic Disease ◽  
Haemorrhagic Disease

Abstract Rabbit haemorrhagic disease virus (RHDV; genotypes GI.1 and GI.2) and European brown hare syndrome virus (EBHSV; genotype GII.1) are caliciviruses belonging to the genus Lagovirus. These viruses pose a serious threat to wild and domestic rabbit and hare populations around the world. In recent years, an expanding genetic diversity has been described within the genus, with recombination events occurring between the different genotypes. Here, we generated and analysed 56 full-genome sequences of RHDV and EBHSV from rabbit and hare livers, collected in Germany between the years 2013 and 2020. We could show that genotype Gl.2 (RHDV-2) almost entirely replaced Gl.1 (classical RHDV) in the German rabbit population. However, GI.1 is still present in Germany and has to be included into disease control and vaccination strategies. Three recombinant strains were identified from rabbit samples that contain the structural genes of genotype Gl.2 and the non-structural genes of genotype Gl.1b. Of special interest is the finding that sequences from two hare samples showed recombination events between structural genes of RHDV Gl.2 and non-structural genes of EBHSV GII.1, a recombination between different genogroups that has not been described before. These findings lead to the assumption that also a recombination of the non-structural genes of RHDV Gl.2 with the structural genes of EBHSV Gll.1 might be possible and therefore increase the potential genetic variability of lagoviruses immensely. Our findings underline the importance of whole genome analysis with next-generation sequencing technology as one of new tools now available for in-depth studies that allow in depth molecular epidemiology with continuous monitoring of the genetic variability of viruses that would otherwise likely stay undetected if only routine diagnostic assays are used.

scholarly journals Genetic variability and phylogenetic analysis of Lagovirus europaeus strains GI.1 (RHDV) and GI.2 (RHDV2) based on the RNA-dependent RNA polymerase (RdRp) coding gene

2020 ◽  
Author(s):  
Beata Hukowska-Szematowicz
Keyword(s):  
Phylogenetic Analysis ◽  
Genetic Variability ◽  
Rna Polymerase ◽  
Genetic Distance ◽  
Disease Virus ◽  
Genetic Material ◽  
Rabbit Haemorrhagic Disease Virus ◽  
Rna Dependent Rna Polymerase ◽  
Rabbit Haemorrhagic Disease ◽  
Haemorrhagic Disease

Lagovirus europaeus GI.1 (RHDV-rabbit haemorrhagic disease virus) and GI.2 (RHDV2-rabbit haemorrhagic disease virus 2), family Caliciviridae, genus Lagovirus, are etiological factors of the rabbit haemorrhagic disease (RHD). This small RNA virus is a great model for tracking the variability and evolution of RNA viruses, because it uses an RNA-dependent RNA polymerase (RdRp) to replicate its own genetic material. This polymerase determines the fidelity and the rates of replication and mutation of the virus, conditioning its adaptation to the environment and even to a new host, and thus influencing evolution of the virus. The aim of this study was to determine the genetic variability and phylogenetic relationships of 105 Lagovirus europaeus strains with different genotypes based on the RdRp gene. The strains came from around the world in the years of 1987–2017. The aforementioned group of 105 strains included 14 strains whose RdRp sequences were obtained and analysed in this study, and the rest were retrieved from GenBank: 74 strains classified as genotype GI.1 (RHDV), 14 as GI.2 (RHDV2), 2 strains of Lagovirus europaeus not assigned to any genotype, and a MRCV strain, the sequences of which were collected from GenBank. Among the 14 strains whose RdRp sequences were obtained in this study, the highest variability was presented in the Austrian 237 strain from 2004. The genetic distance between the Austrian 237 strain and the remaining thirteen analysed strains ranged from 0.117 to 0.123 (from 11.7% to 12.3% nucleotide substitutions). The lowest variability, however, was recorded for Hungarian, Czech and Austrian strains. On the phylogenetic tree, the 14 analysed strains were allocated into GI.1c (G2), GI.1d (G3-G5) and GI.1a (RHDVa). Analysis of the genetic variability of the 105 strains of Lagovirus europaeus indicated a growing genetic distance between the strains, both in time and location. Phylogenetic analysis showed a division of the strains into seven groups, dictated by the chronology, geographical location and evolutionary events in the history of the virus, such as mutations and recombinations.

scholarly journals Structural, antigenic and immunogenic relationships between European brown hare syndrome virus and rabbit haemorrhagic disease virus.

1997 ◽  
Vol 78 (11) ◽  
pp. 2803-2811 ◽  
Author(s):  
S Laurent ◽  
G Le Gall ◽  
M F Madelaine ◽  
D Rasschaert ◽  
J F Vautherot
Keyword(s):  
Disease Virus ◽  
Brown Hare ◽  
Rabbit Haemorrhagic Disease Virus ◽  
European Brown Hare ◽  
Rabbit Haemorrhagic Disease ◽  
European Brown Hare Syndrome ◽  
Haemorrhagic Disease

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

2001 ◽  
Vol 356 (1411) ◽  
pp. 1087-1095 ◽  
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.

Distribution of Rabbit Haemorrhagic Disease Virus RNA in Experimentally Infected Rabbits

2001 ◽  
Vol 124 (2-3) ◽  
pp. 134-141 ◽  
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

scholarly journals Molecular epidemiology of Rabbit haemorrhagic disease virus

2002 ◽  
Vol 83 (10) ◽  
pp. 2461-2467 ◽  
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.

scholarly journals 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 ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 553 ◽  
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.

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

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 441 ◽  
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.

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

2005 ◽  
Vol 32 (2) ◽  
pp. 139 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document