New variant of rabbit hemorrhagic disease virus, Portugal, 2012-2013.
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ABSTRACT:
SUBMITTER: Abrantes J
PROVIDER: S-EPMC3837648 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The introduction of rabbit hemorrhagic disease virus (RHDV) into Australia and New Zealand during the 1990s as a means of controlling feral rabbits is an important case study in viral emergence. Both epidemics are exceptional in that the founder viruses share an origin and the timing of their release is known, providing a unique opportunity to compare the evolution of a single virus in distinct naive populations. We examined the evolution and spread of RHDV in Australia and New Zealand through a genome-wide evolutionary analysis, including data from 28 newly sequenced RHDV field isolates. Following the release of the Australian inoculum strain into New Zealand, no subsequent mixing of the populations occurred, with viruses from both countries forming distinct groups. Strikingly, the rate of evolution in the capsid gene was higher in the Australian viruses than in those from New Zealand, most likely due to the presence of transient deleterious mutations in the former. However, estimates of both substitution rates and population dynamics were strongly sample dependent, such that small changes in sample composition had an important impact on evolutionary parameters. Phylogeographic analysis revealed a clear spatial structure in the Australian RHDV strains, with a major division between those viruses from western and eastern states. Importantly, RHDV sequences from the state where the virus was first released, South Australia, had the greatest diversity and were diffuse throughout both geographic lineages, such that this region was likely a source population for the subsequent spread of the virus across the country.Most studies of viral emergence lack detailed knowledge about which strains were founders for the outbreak or when these events occurred. Hence, the human-mediated introduction of rabbit hemorrhagic disease virus (RHDV) into Australia and New Zealand from known starting stocks provides a unique opportunity to understand viral evolution and emergence. Within Australia, we revealed a major phylogenetic division between viruses sampled from the east and west of the country, with both regions likely seeded by viruses from South Australia. Despite their common origins, marked differences in evolutionary rates were observed between the Australian and New Zealand RHDV, which led to conflicting conclusions about population growth rates. An analysis of mutational patterns suggested that evolutionary rates have been elevated in the Australian viruses, at least in part due to the presence of low-fitness (deleterious) variants that have yet to be selectively purged.
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Project description:To determine the origin, phylogenetic relationships, and evolutionary dynamics of rabbit hemorrhagic disease virus (RHDV), we examined 210 partial and complete capsid gene nucleotide sequences. Using a Bayesian Markov chain Monte Carlo approach, we estimated that these sequences evolved at a rate of 3.9 x 10(-4) to 11.9 x 10(-4) nucleotide substitutions per site per year. This rate was consistent across subsets of data, was robust in response to recombination, and casts doubt on the provenance of viral strains isolated from the 1950s to the 1970s, which share strong sequence similarity to modern isolates. Using the same analysis, we inferred that the time to the most recent common ancestor for a joint group of RHDV and rabbit calicivirus sequences was <550 years ago and was <150 years ago for the RHDV isolates that have spread around the world since 1984. Importantly, multiple lineages of RHDV were clearly circulating before the major Chinese outbreak of 1984, a finding indicative of an early evolution of RHDV virulence. Four phylogenetic groups within RHDV were defined and analyzed separately. Each group shared a common ancestor in the mid-1960s or earlier, and each showed an expansion of populations starting before 1984. Notably, the group characterized by the antigenic variant RHDVa harbors the greatest genetic diversity, compatible with an elevated fitness. Overall, we contend that the high virulence of RHDV likely evolved once in the early part of the 20th century, well before the documented emergence of rabbit hemorrhagic disease in 1984.
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Project description:The rabbit hemorrhagic disease virus (RHDV) represents the causative agent of a highly contagious disease in rabbits that is often associated with high mortality. Because of the lack of a suitable cell culture system for RHDV, the pathogenic mechanism and replication of RHDV remains unclear. In order to analyze the pathogenic mechanism of RHDV to rabbits, we used New Zealand white rabbits infected with RHDV, collected liver tissues 32 hours after infection, and used TMT labeling for LC-MS analysis. Subsequently, it was compared and analyzed with the protein data of the liver tissue of the uninfected rabbits. Perform bioinformatics analysis on significantly different proteins. Finally, comprehensively analyze the influence of RHDV on host protein and pathway expression levels. This study provides clues to clarify the pathogenic mechanism of RHDV in rabbits.
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Project description:Twenty-three of 42 European rabbits (Oryctolagus cuniculus), belonging to the same rabbit colony, died in March 2020 (55% mortality) in Chiba prefecture, Japan. The disease course was extremely acute without indicators of death or hemorrhage. Necropsy revealed liver swelling, discoloration, cloudiness and fragility, and pulmonary edema. Histologically, severe hepatocellular necrosis (mainly peripheral) and intra-glomerular capillary hyalin thrombi were observed. On molecular-biological examination, reverse transcription polymerase chain reaction analysis of RNA from tissues detected a rabbit hemorrhagic disease virus, confirmed as a RHDV-2 VP60 fragment, which shared 99.42% nucleotide identity with the homologous fragment of RHDV-2 German isolate by nucleotide sequence analysis. This report shows the outbreak of rabbit hemorrhagic disease caused by RHDV-2, an emerging infectious disease, in Japan.
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