Reactivity of selected markers of innate and adaptive immunity in rabbits experimentally infected with antigenic variants of RHD (Lagovirus europaeus/GI.1a).
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ABSTRACT:
SUBMITTER: Niedzwiedzka-Rystwej P
PROVIDER: S-EPMC8791865 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The rabbit caliciviruses Lagovirus europaeus GI.1 and GI.2 both cause acute necrotizing hepatitis in European rabbits (Oryctolagus cuniculus). Whilst GI.2 is highly virulent in both young and adult rabbits, rabbits younger than eight weeks of age are highly resistant to disease caused by GI.1, although they are still permissive to infection and viral replication. To investigate the underlying mechanism(s) of this age related resistance to GI.1, we compared liver transcriptomes of young rabbits infected with GI.1 to those of adult rabbits infected with GI.1 and young rabbits infected with GI.2. Our data suggest that kittens have constitutively heightened innate immune responses compared to adult rabbits, particularly associated with increased expression of major histocompatibility class II molecules and activity of natural killer cells, macrophages, and cholangiocytes. This enables them to respond more rapidly to GI.1 infection than adult rabbits and thus limit virus-induced pathology. In contrast, these responses were not fully developed during GI.2 infection. We speculate that the observed downregulation of multiple genes associated with innate immunity in kittens during GI.2 infection may be due to virally-mediated immunomodulation, permitting fatal disease to develop. Our study provides insight into the fundamental host⁻pathogen interactions responsible for the differences in age-related susceptibility, which likely plays a critical role in defining the success of GI.2 in outcompeting GI.1 in the field.
| S-EPMC6163550 | biostudies-literature
Project description:Rabbit hemorrhagic disease (RHD) causes high mortality and morbidity in European rabbits (Oryctolagus cuniculus). In Africa, the presence of the causative agent, the rabbit hemorrhagic disease virus (RHDV), was first confirmed in 1992 (genotype Lagovirus europaeus/GI.1). In 2015, the new genotype Lagovirus europaeus/GI.2 (RHDV2/b) was detected in Tunisia. Currently, GI.2 strains are present in several North and Sub-Saharan African countries. Considerable economic losses have been observed in industrial and traditional African rabbitries due to RHDV. Like other RNA viruses, this virus presents high recombination rates, with the emergence of GI.2 being associated with a recombinant strain. Recombination events have been detected with both pathogenic (GI.1b and GII.1) and benign (GI.3 and GI.4) strains. We obtained complete genome sequences of Tunisian GI.2 strains collected between 2018 and 2020 and carried out phylogenetic analyses. The results revealed that Tunisian strains are GI.3P-GI.2 strains that were most likely introduced from Europe. In addition, the results support the occurrence of multiple introductions of GI.2 into Africa, stressing the need for characterizing complete genome sequences of the circulating lagoviruses to uncover their origin. Continued monitoring and control of rabbit trade will grant a better containment of the disease and reduce the disease-associated economic losses.
| S-EPMC8471427 | biostudies-literature
Project description:Rabbit haemorrhagic disease is a viral disease that emerged in the 1980s and causes high mortality and morbidity in the European rabbit (Oryctolagus cuniculus). In 2010, a new genotype of the rabbit haemorrhagic disease virus emerged and replaced the former circulating Lagovirus europaeus/GI.1 strains. Several recombination events have been reported for the new genotype Lagovirus europaeus/GI.2, with pathogenic (variants GI.1a and GI.1b) and benign (genotype GI.4) strains that served as donors for the non-structural part while GI.2 composed the structural part; another recombination event has also been described at the p16/p23 junction involving GI.4 strains. In this study, we analysed new complete coding sequences of four benign GI.3 strains and four GI.2 strains. Phylogenetic and recombination detection analyses revealed that the first GI.2 strains, considered as non-recombinant, resulted from a recombination event between GI.3 and GI.2, with GI.3 as the major donor for the non-structural part and GI.2 for the structural part. Our results indicate that recombination contributed to the emergence, persistence and dissemination of GI.2 as a pathogenic form and that all described GI.2 strains so far are the product of recombination. This highlights the need to study full-genomic sequences of lagoviruses to understand their emergence and evolution.
| S-EPMC7468141 | biostudies-literature
Project description:Lagovirus europaeus GI.2, also known as RHDV2 or RHDVb, is an emerging virus that causes rabbit haemorrhagic disease (RHD) in European rabbits (Oryctolagus cuniculus). In contrast to L. europaeus GI.1 (or RHDV/RHDVa) viruses that are only pathogenic for adults, GI.2 causes clinical disease in both adults and kittens. However, detailed descriptions of the pathology of this virus that may provide insight into its pathogenicity and emergence are lacking. Using an Australian GI.2 field strain isolated in 2015, we provide the first detailed description of pathology, viral antigen distribution and tissue load of GI.2 in adult and 5-week old New Zealand white rabbits using histology, immunohistochemistry and RT-qPCR. Liver was the target organ, but in contrast to GI.1 viruses, lesions and inflammatory responses did not differ between adults and kittens. Lymphocytic inflammation, proposed to be protective in kittens infected with GI.1, was notably absent. We also present the first descriptions of bone marrow changes in RHD, including decreased myeloid-to-erythroid ratio. Consistent with other pathogenic lagoviruses, intracellular viral antigen was demonstrated in hepatocytes and cells of the mononuclear phagocytic system. In terminal stages of disease, viral loads were highest in liver, serum and spleen. Despite the small sample size, our data suggest that unlike early European GI.2 strains, the pathogenicity of the Australian GI.2 virus is similar to GI.1 viruses. Additionally, GI.2 was fatal for all (n?=?5) inoculated kittens in this study. This may significantly alter RHD epidemiology in the field, and may impact biocontrol programs for invasive rabbits in Australia where GI.1 viruses are intentionally released.
| S-EPMC5987473 | biostudies-literature
Project description:BACKGROUND:Prior to 2010, the lagoviruses that cause rabbit hemorrhagic disease (RHD) in European rabbits (Oryctolagus cuniculus) and European brown hare syndrome (EBHS) in hares (Lepus spp.) were generally genus-specific. However, in 2010, rabbit hemorrhagic disease virus 2 (RHDV2), also known as Lagovirus europaeus GI.2, emerged and had the distinguishing ability to cause disease in both rabbits and certain hare species. The mountain hare (Lepus timidus) is native to Sweden and is susceptible to European brown hare syndrome virus (EBHSV), also called Lagovirus europaeus GII.1. While most mountain hare populations are found on the mainland, isolated populations also exist on islands. Here we investigate a mortality event in mountain hares on the small island of Hallands Väderö where other leporid species, including rabbits, are absent. RESULTS:Post-mortem and microscopic examination of three mountain hare carcasses collected from early November 2016 to mid-March 2017 revealed acute hepatic necrosis consistent with pathogenic lagovirus infection. Using immunohistochemistry, lagoviral capsid antigen was visualized within lesions, both in hepatocytes and macrophages. Genotyping and immunotyping of the virus independently confirmed infection with L. europaeus GI.2, not GII.1. Phylogenetic analyses of the vp60 gene grouped mountain hare strains together with a rabbit strain from an outbreak of GI.2 in July 2016, collected approximately 50?km away on the mainland. CONCLUSIONS:This is the first documented infection of GI.2 in mountain hares and further expands the host range of GI.2. Lesions and tissue distribution mimic those of GII.1 in mountain hares. The virus was most likely initially introduced from a concurrent, large-scale GI.2 outbreak in rabbits on the adjacent mainland, providing another example of how readily this virus can spread. The mortality event in mountain hares lasted for at least 4.5?months in the absence of rabbits, which would have required virus circulation among mountain hares, environmental persistence and/or multiple introductions. This marks the fourth Lepus species that can succumb to GI.2 infection, suggesting that susceptibility to GI.2 may be common in Lepus species. Measures to minimize the spread of GI.2 to vulnerable Lepus populations therefore are prudent.
| S-EPMC6258167 | biostudies-literature
Project description:BackgroundRabbit haemorrhagic disease virus Lagovirus europaeus/GI.1d variant (GI.1d/RHDV) was identified in 1990 in France, and until the emergence of the new genotype GI.2, it was the main variant circulating in the country. The early stages of RHDV infection have been described in a few studies of rabbits experimentally infected with earlier strains, but no information was given on the minimum infective dose. We report the genomic and phenotypic characterisation of a GI.1d/RHDV strain collected in 2000 in France (GI.1d/00-21).ResultsWe performed in vivo assays in rabbits to study virus replication kinetics in several tissues at the early stage of infection, and to estimate the minimum infective dose. Four tested doses, negligible (10- 1 viral genome copies), low (104), high (107) and very high (1011) were quantified using a method combining density gradient centrifugation of the viral particles and an RT-qPCR technique developed to quantify genomic RNA (gRNA). The GI.1d/00-21 genome showed the same genomic organisation as other lagoviruses; however, a substitution in the 5' untranslated region and a change in the potential p23/2C-like helicase cleavage site were observed. We showed that the liver of one of the two rabbits inoculated via the oral route was infected at 16 h post-infection and all tissues at 39 h post-infection. GI.1d/00-21 induced classical RHD signs (depression) and lesions (haemorrhage and splenomegaly). Although infective dose estimation should be interpreted with caution, the minimum infective dose that infected an inoculated rabbit was lower or equal to 104 gRNA copies, whereas between 104 and 107 gRNA copies were required to also induce mortality.ConclusionsThese results provide a better understanding of GI.1d/RHDV infection in rabbits. The genome analysis showed a newly observed mutation in the 5' untranslated region of a lagovirus, whose role remains unknown. The phenotypic analysis showed that the pathogenicity of GI.1d/00-21 and the replication kinetics in infected organs were close to those reported for the original GI.1 strains, and could not alone explain the observed selective advantage of the GI.1d strains. Determining the minimum dose of viral particles required to cause mortality in rabbits is an important input for in vivo studies.
| S-EPMC8320185 | biostudies-literature
Project description:Rabbit haemorrhagic disease virus (RHDV) is a lagovirus that causes rabbit haemorrhagic disease (RHD) in European rabbits (Oryctolagus cuniculus). In 2010, a new genotype called RHDV2 emerged in France. It exhibits a larger host range than classical RHDV strains by sporadically infecting different hare species, including the European hare (Lepus europaeus). Phylogenetic analyses revealed that closely related RHDV2 strains circulate locally in both hares and rabbits, and therefore that RHDV2 strains infecting hares do not belong to a lineage that has evolved only in this species. We showed that RHDV2 is widely distributed in France and that it was responsible for more than a third of cases of lagovirus disease in European hare populations in 2015. The oldest RHDV2 positive hare was sampled in November 2013 and we reported two hares co-infected by EBHSV and RHDV2. All together, our results raise important epidemiological and evolutionary issues. In particular, along with the potential emergence of recombinant EBHSV/RHDV2 strains in hares, the enlargement of the host range changes the host population structure of RHDV2 and may alter the impact of the virus on rabbit and hare populations.
| S-EPMC5660455 | biostudies-literature
Project description:In the early 1980s, a highly contagious viral hemorrhagic fever in rabbits (Oryctolagus cuniculus) emerged, causing a very high rate of mortality in these animals. Since the initial occurrence of the rabbit hemorrhagic disease virus (RHDV), several hundred million rabbits have died after infection. The emergence of genetically-different virus variants (RHDV GI.1 and GI.2) indicated the very high variability of RHDV. Moreover, with these variants, the host range broadened to hare species (Lepus). The circulation of RHDV genotypes displays different virulences and a limited induction of cross-protective immunity. Interestingly, juvenile rabbits (<9 weeks of age) with an immature immune system display a general resistance to RHDV GI.1, and a limited resistance to RHDV GI.2 strains, whereas less than 3% of adult rabbits survive an infection by either RHDV GI.1. or GI.2. Several not-yet fully understood phenomena characterize the RHD. A very low infection dose followed by an extremely rapid viral replication could be simplified to the induction of a disseminated intravascular coagulopathy (DIC), a severe loss of lymphocytes-especially T-cells-and death within 36 to 72 h post infection. On the other hand, in animals surviving the infection or after vaccination, very high titers of RHDV-neutralizing antibodies were induced. Several studies have been conducted in order to deepen the knowledge about the virus' genetics, epidemiology, RHDV-induced pathology, and the anti-RHDV immune responses of rabbits in order to understand the phenomenon of the juvenile resistance to this virus. Moreover, several approaches have been used to produce efficient vaccines in order to prevent an infection with RHDV. In this review, we discuss the current knowledge about anti-RHDV resistance and immunity, RHDV vaccination, and the further need to establish rationally-based RHDV vaccines.
| S-EPMC8002203 | biostudies-literature
Project description:Resistance to Rabbit Haemorrhagic Disease (RHD) virus in wild Australian rabbits: comparison of susceptible and resistant individuals using a genome-wide approach
| PRJEB20958 | ENA
Project description:We report the full genome sequence of the non-pathogenic rabbit lagovirus Lagovirus europaeus/GI.3/O cun/FR/2006/06-11 (GI.3/06-11), collected from a healthy French domestic rabbit in 2006, and initially described as 06-11 strain. The sequence reveals a genomic organization similar to lagoviruses. It was 7,436 bases long and contained two open reading frames (ORF). A dipeptide variation at the potential p23/2C-like helicase cleavage site (EE instead of ED) was observed, a feature only shared with non-recombinant pathogenic lagoviruses in GI.2 and with two European brown hare syndrome viruses (EBHSV) collected in 1982 in Sweden. GI.3/06-11 has only one initiation codon at the beginning of the ORF2 like the avirulent Italian rabbit calicivirus (RCV) and EBHSV. Previous genetic analyses based on the capsid gene sequences showed that GI.3/06-11 was closer to the RCV and pathogenic lagoviruses GI.1 strains than other lagoviruses. This study, by revealing that GI.3/06-11 genome sequence significantly clustered with pathogenic GI.2 strains, gives prominence of new genetic relationship among lagoviruses and should contribute to understand the emergence of pathogenic strains.
| S-EPMC6132933 | biostudies-literature