Overcoming species barriers: an outbreak of Lagovirus europaeus GI.2/RHDV2 in an isolated population of mountain hares (Lepus timidus)

Abstract

BackgroundPrior 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.ResultsPost-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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (10.1186/s12917-018-1694-7) contains supplementary material, which is available to authorized users.

Recombination at the emergence of the pathogenic rabbit haemorrhagic disease virus Lagovirus europaeus/GI.2

“…Leeks and colleagues established a link between co-infection and viral diversity, as more diverse populations can produce more virulent infections and better adapt to new hosts 60 . This might explain the array of hare species infected by GI.2 [13][14][15][16][17] , which constitutes a novelty in relation to GI.1.…”

“…GI.2 was identified as a novel pathogenic form of lagovirus in France in 2010 8 . Field observations and further characterisation of the strains revealed unique characteristics in comparison with former strains such as the ability to cross the species boundaries [13][14][15][16][17] and to kill young rabbits 11,12 . Previous studies also revealed the occurrence of recombination of GI.2 strains with non-pathogenic (GI.4) and pathogenic (GI.1a and GI.1b) strains [24][25][26] , showing an important role of recombination in generating diversity in GI.2 and confirming the high capacity of recombination within lagoviruses.…”

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

“…Furthermore, RHDV2 can cause infection not only in young rabbits, including those aged 11 days (Dalton et al, 2012), which used to be considered resistant to the old RHDV genotypes; but also in vaccinated rabbits (Le Gall-Recule et al, 2013), which has also been confirmed in Poland (Fitzner & Niedbalski, 2018). It was also evidenced that RHDV2 causes diseases in other lagomorph species, including the Sardinian Cape hare (Lepus capensis mediterraneus) (Puggioni et al, 2013), Corsican (Italian) hare (Lepus corsicanus) (Camarda et al, 2014), Iberian hare (Lepus granatensis) (Lopes et al, 2014) and European hare (Lepus europaeus) (Hall et al, 2017), and recently even in the mountain hare (Lepus timidus) (Neimanis et al, 2018) and hares in England (Bell et al, 2019), unlike RHDV and RHDVa, which are believed to be characteristic for the European rabbit (Oryctolagus cuniculus). The latest case of infection is the sixth Lepus species to be infected with RHDV2, which suggests that the susceptibility to RHDV2 can be widespread among the Lepus species (Neimanis et al, 2018;Bell et al, 2019).…”

“…It was also evidenced that RHDV2 causes diseases in other lagomorph species, including the Sardinian Cape hare (Lepus capensis mediterraneus) (Puggioni et al, 2013), Corsican (Italian) hare (Lepus corsicanus) (Camarda et al, 2014), Iberian hare (Lepus granatensis) (Lopes et al, 2014) and European hare (Lepus europaeus) (Hall et al, 2017), and recently even in the mountain hare (Lepus timidus) (Neimanis et al, 2018) and hares in England (Bell et al, 2019), unlike RHDV and RHDVa, which are believed to be characteristic for the European rabbit (Oryctolagus cuniculus). The latest case of infection is the sixth Lepus species to be infected with RHDV2, which suggests that the susceptibility to RHDV2 can be widespread among the Lepus species (Neimanis et al, 2018;Bell et al, 2019). Holms and Grenfell (Holms & Grenfell, 2009) explain that the occurrence of new variants of the virus in the wild is the result of four factors: (1) adaptive evolution of the host's genes that engage in the most thorough interaction with the host's immune response, and react at the "host-pathogen" level, (2) interaction among the locally circulating viruses, (3) possible outbreak dynamics in time and space, and (4) disease spread control methods.…”

Retrospective serological analysis reveals presence of the emerging lagovirus RHDV2 in Australia in wild rabbits at least five months prior to its first detection

“…RHDV2 is a new lagovirus that was first reported in Europe in 2010 (Dalton et al, ; Le Gall‐Recule et al, ). It is not only genetically distinct from RHDV and RHDVa but, unlike RHDV and RHDVa, is also able to cause highly fatal disease in very young rabbits (Dalton, Nicieza, Abrantes, Esteves, & Parra, ; Neimanis, Pettersson, Huang, Gavier‐Widen, & Strive, ) and is capable of fatally infecting several species of hares (Camarda et al, ; Hall et al, ; Le Gall‐Recule et al, ; Neimanis, Ahola, et al, ; Puggioni et al, ; Velarde et al, ). Since its arrival in Australia, RHDV2 has become the dominant strain circulating in the field, seemingly replacing older RHDV strains and accounting for the majority of reported cases in wild and domestic rabbits (Mahar, Hall, et al, ).…”