scholarly journals Frequent Intergenotypic Recombination Between the Non-Structural and Structural Genes is a Major Driver of Epidemiological Fitness in Caliciviruses

2021 ◽  
Author(s):  
Jackie E Mahar ◽  
Maria Jenckel ◽  
Nina Huang ◽  
Elena Smertina ◽  
Edward C Holmes ◽  
...  

Abstract The diversity of lagoviruses (Caliciviridae) in Australia has increased considerably in recent years. By the end of 2017, five variants from three viral genotypes were present in populations of Australian rabbits, while prior to 2014 only two variants were known. To understand the evolutionary interactions among these lagovirus variants we monitored their geographical distribution and relative incidence over time in a continental-scale competition study. Within three years of the incursion of rabbit haemorrhagic disease virus 2 (RHDV2, denoted genotype GI.1bP-GI.2 [polymerase genotype]P-[capsid genotype]) into Australia, two novel recombinant lagovirus variants emerged: RHDV2-4e (genotype GI.4eP-GI.2) in New South Wales and RHDV2-4c (genotype GI.4cP-GI.2) in Victoria. Although both novel recombinants contain non-structural genes related to those from benign, rabbit-specific, enterotropic viruses, these variants were recovered from the livers of both rabbits and hares that had died acutely. This suggests that the determinants of host and tissue tropism for lagoviruses are associated with the structural genes, and that tropism is intricately connected with pathogenicity. Phylogenetic analyses demonstrated that the RHDV2-4c recombinant emerged independently on multiple occasions, with five distinct lineages observed. Both the new RHDV2-4e and 4c recombinant variants replaced the previous dominant parental RHDV2 (genotype GI.1bP-GI.2) in their respective geographical areas, despite sharing an identical or near-identical (i.e. single amino acid change) VP60 major capsid protein with the parental virus. This suggests that the observed replacement by these recombinants was not driven by antigenic variation in VP60, implicating the non-structural genes as key drivers of epidemiological fitness. Molecular clock estimates place the RHDV2-4e recombination event in early to mid-2015, while the five RHDV2-4c recombination events occurred from late 2015 through to early 2017. The emergence of at least six viable recombinant variants within a two-year period highlights the high frequency of these events, detectable only through intensive surveillance, and demonstrates the importance of recombination in lagovirus evolution.

2021 ◽  
Author(s):  
Jackie E Mahar ◽  
Maria Jenckel ◽  
Nina Huang ◽  
Elena Smertina ◽  
Edward C Holmes ◽  
...  

AbstractThe diversity of lagoviruses (Caliciviridae) in Australia has increased considerably. By the end of 2017, five variants from three viral genotypes were present in populations of Australian rabbits, while prior to 2014 only two variants were known. To understand the interactions between these lagovirus variants we monitored their geographical distribution and relative incidence over time through a landscape-scale competition study, and from this, revealed potential drivers of epidemiological fitness. Within three years of the arrival of GI.1bP-GI.2 (RHDV2) into Australia, we observed the emergence of two novel recombinant lagovirus variants, GI.4eP-GI.2 (4e-recombinant) in New South Wales and GI.4cP-GI.2 (4c-recombinant) in Victoria. Although both novel recombinants contain the non-structural genes from benign, rabbit-specific, enterotropic viruses, these variants were recovered from the livers of both rabbits and hares that had died acutely. This suggests that determinants of host and tissue tropism for lagoviruses are associated with the structural genes, and that tropism is intricately connected with pathogenicity. Phylogenetic analyses demonstrated that the 4c-recombinant emerged independently on multiple occasions, with five distinct lineages observed. Both new recombinant variants replaced the previous dominant parental RHDV2 in their respective geographical areas, despite sharing an identical or near-identical (i.e., single amino acid change) major capsid protein with the parental virus. This suggests that epidemiological fitness of these recombinants was not driven by antigenic variation in the capsid, implicating the non-structural genes as key drivers of epidemiological fitness. Molecular clock estimates place the GI4.e recombination event in early to mid-2015, while the five GI.4c recombination events occurred from late 2015 through to early 2017. The emergence of at least six viable recombinant variants within a two-year period highlights an unprecedented frequency of these events, detectable only due to intensive surveillance, and demonstrates the importance of recombination in lagovirus evolution.


2014 ◽  
Vol 41 (2) ◽  
pp. 95 ◽  
Author(s):  
Jerry Olsen ◽  
Brian Cooke ◽  
Susan Trost ◽  
David Judge

Context Some ecologists argue that nesting success and abundance of wedge-tailed eagles (Aquila audax) are strongly linked to the abundance of introduced wild rabbits (Oryctolagus cuniculus). Consequently, concerns were expressed about eagle population viability when the biological control agent rabbit haemorrhagic disease virus (RHDV) heavily reduced rabbit numbers. However, observations following the spread of rabbit haemorrhagic disease (RHD) in Australia and Spain (where Aquila adalberti is an equivalent of A. audax) question this assertion. Eagle numbers did not fall even though rabbits declined regionally by up to 90% in both countries. Aims To reconsider the assumption of a strong link between rabbit abundance and wedge-tailed eagle breeding and population maintenance. Dispelling misconceptions, if any, about the eagles’ dependence on rabbits would benefit the future management of both eagles and rabbits. Methods We reviewed the literature associated with claims that eagles were heavily dependent on rabbits and asked whether these views could be substantiated given the lack of changes in eagle abundance following the spread of RHD. Data on eagle egg-clutch size and nesting success were also reviewed. Conclusions There is little evidence that eagles depend heavily on rabbits as prey. Instead, as rabbits decline, more kangaroos, reptiles and birds are eaten, partly because more native prey becomes available. Eagles have a high proportion of rabbits in their diets mainly where degradation of natural ecosystems, including that caused by rabbits, results in native prey being rare or unavailable. There has been minimal variation in average clutch size following major perturbations in rabbit population size. Implications Rather than perpetuating the idea that high populations of rabbits are needed for wedge-tailed eagle conservation, resources would be better re-directed into understanding continental-scale eagle population dynamics. This would provide a more rational framework to assist decisions on future biological control agents for rabbits.


2012 ◽  
Vol 59 (4) ◽  
Author(s):  
Beata Hukowska-Szematowicz ◽  
Beata Tokarz-Deptuła ◽  
Wiesław Deptuła

Rabbit haemorrhagic disease virus (RHDV) belongs to the family Caliciviridae and is the etiological agent of the haemorrhagic disease, also known as rabbit plague. Its genome is a linear single-stranded (ss) RNA of 7437 nucleotides and the capsid is built from a single structural protein VP60. In connection with the discovery of new RHDV strains, there is a constant need to investigate the genetic variation of this virus and perform phylogenetic analyses which may show the evolutionary relationships among the RHDV strains. Studies on the divergence of RHDV have shown that it is genetically quite stable, although recent observations indicate that some new RHDV strains, significantly different from the original RHDV subtype and the new RHDVa subtype, are appearing. These latest findings suggest that a new group of RHDV strains has evolved. The present review summarizes the current knowledge on the genetic variation and the latest achievements in phylogenetic analyses of RHDV strains isolated in various countries.


2019 ◽  
Vol 48 (1) ◽  
pp. 316-331 ◽  
Author(s):  
Lisa Kesselring ◽  
Csaba Miskey ◽  
Cecilia Zuliani ◽  
Irma Querques ◽  
Vladimir Kapitonov ◽  
...  

Abstract The Sleeping Beauty (SB) transposon is an advanced tool for genetic engineering and a useful model to investigate cut-and-paste DNA transposition in vertebrate cells. Here, we identify novel SB transposase mutants that display efficient and canonical excision but practically unmeasurable genomic re-integration. Based on phylogenetic analyses, we establish compensating amino acid replacements that fully rescue the integration defect of these mutants, suggesting epistasis between these amino acid residues. We further show that the transposons excised by the exc+/int− transposase mutants form extrachromosomal circles that cannot undergo a further round of transposition, thereby representing dead-end products of the excision reaction. Finally, we demonstrate the utility of the exc+/int− transposase in cassette removal for the generation of reprogramming factor-free induced pluripotent stem cells. Lack of genomic integration and formation of transposon circles following excision is reminiscent of signal sequence removal during V(D)J recombination, and implies that cut-and-paste DNA transposition can be converted to a unidirectional process by a single amino acid change.


2003 ◽  
Vol 30 (1) ◽  
pp. 49 ◽  
Author(s):  
Piran C. L. White ◽  
Geraldine Newton-Cross ◽  
Michael Gray ◽  
Roland Ashford ◽  
Catherine White ◽  
...  

Successful control of European rabbit (Oryctolagus cuniculus) populations in Australia has been achieved with the use of disease, initially myxomatosis and more recently rabbit haemorrhagic disease (RHD). Predicting the effectiveness of disease as a control agent depends on understanding the spatial and social organisation of its host population. We radio-tracked 37 rabbits from adjacent burrow systems during May and June 1999. Surface-dwelling rabbits had larger home ranges and core areas and a higher proportion of vegetation cover in their ranges than warren-based rabbits. Interactions between rabbit dyads from the same warren showed greater range overlap than those involving rabbits from different warrens and those involving itinerants. Static interaction was high and positive for intra-warren dyads, but low and negative for inter-warren, warren–surface and surface–surface dyads. These patterns of range use and interaction behaviour create a hierarchical contact and transmission structure within the rabbit population that is likely to vary according to external factors such as population density, resource availability, season, climate and the environment. Quantifying these links between the environment and the transmission process is important to increase our understanding of RHD as an effective management tool for rabbit populations.


2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Kevin P Szillat ◽  
Dirk Höper ◽  
Martin Beer ◽  
Patricia König

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.


1999 ◽  
Vol 26 (1) ◽  
pp. 69 ◽  
Author(s):  
Glen Saunders ◽  
David Choquenot ◽  
John McIlroy ◽  
Rossanne Packwood

Quarterly spotlight counts of rabbits were conducted at three sites in central-western New South Wales. These counts commenced two years before the arrival of rabbit haemorrhagic disease (RHD) in the winter of 1996. The existing data on quarterly rates of change in rabbit abundance for the three populations provided a unique opportunity to study the effects of RHD on rabbit demography. Prior to the arrival of RHD, all three populations underwent phases of sequential increase and decrease in each year. On the basis of these patterns, RHD had a variable influence on the demography of the three rabbit populations. In 1996–97, the density of two populations declined over an expected period of increase, while at the third site the density increased as expected from pre-RHD patterns. Twelve months after their failure to generate expected positive rates of increase the two affected populations had returned to the normal sequence of increases and decreases in density although still at comparatively low numbers.


2000 ◽  
Vol 27 (6) ◽  
pp. 613 ◽  
Author(s):  
Andrew Moriarty ◽  
Glen Saunders ◽  
Barry J. Richardson

Mortality of radio-tagged adult rabbits (Oryctolagus cuniculus) (n = 274) was monitored for one year in central-western New South Wales. The overall mortality rate was 82%. Predation was the most important and consistent cause of adult rabbit mortality, accounting for 44% of the total number of rabbits, followed by Rabbit Haemorrhagic Disease (RHD) (16%), myxomatosis (9%), unknown causes (9%), and enteritis/peritonitis (2%). Foxes were the most important predators, accounting for 28% of radio-tagged rabbits. Medium to large birds of prey were less important, accounting for 10%, followed by cats, which were responsible for 6% of the deaths of radio-collared rabbits. Myxomatosis outbreaks occurred in February/March and November–January. An RHD outbreak occurred during July, with 40% of the adult rabbit population being killed. The number of male and female radio-collared adult rabbits killed by each mortality agent throughout the year was similar. The proportions of warren-dwelling rabbits and surface-dwelling, solitary rabbits killed were similar overall; however, a significantly higher number of warren-dwelling rabbits were killed by myxomatosis and a significantly higher number of surface-dwelling rabbits were killed by RHD.


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