The discovery of three new hare lagoviruses reveals unexplored viral diversity in this genus

Abstract

Our knowledge of mammalian viruses has been strongly skewed toward those that cause disease in humans and animals. However, recent metagenomic studies indicate that most apparently healthy organisms carry viruses, and that these seemingly benign viruses may comprise the bulk of virus diversity. The bias toward studying viruses associated with overt disease is apparent in the lagoviruses (family Caliciviridae) that infect rabbits and hares: although most attention has been directed toward the highly pathogenic members of this genus - the rabbit haemorrhagic disease virus and European brown hare syndrome virus - a number of benign lagoviruses have also been identified. To determine whether wild European brown hares in Australia might also carry undetected benign viruses, we used a meta-transcriptomics approach to explore the gut and liver RNA viromes of these invasive animals. This led to the discovery of three new lagoviruses. While one of the three viruses was only detected in a single hare, the other two viruses were detected in 20% of all hares tested. All three viruses were most closely related to other hare lagoviruses, but were highly distinct from both known viruses and each other. We also found evidence for complex recombination events in these viruses, which, combined with their phylogenetic distribution, suggests that there is likely extensive unsampled diversity in this genus. Additional metagenomic studies of hares and other species are clearly needed to fill gaps in the lagovirus phylogeny and hence better understand the evolutionary history of this important group of mammalian viruses.

Viral Disease in Lagomorphs: A Molecular Perspective

“…The identification of hare caliciviruses (HaCV) GII.2 related to EBHSV have further shown the large diversity and complexity that exists for this genera of virus [129][130][131][132]. HaCV has been detected in duodenum or faeces of healthy hares in Italy, France, Austria, Germany and Australia (also weakly detected in liver) [129][130][131][132][133].…”

“…The identification of hare caliciviruses (HaCV) GII.2 related to EBHSV have further shown the large diversity and complexity that exists for this genera of virus [129][130][131][132]. HaCV has been detected in duodenum or faeces of healthy hares in Italy, France, Austria, Germany and Australia (also weakly detected in liver) [129][130][131][132][133]. The virus is considered to be non-pathogenic based the health status of animals from which the samples were obtained and the target organ, however, virulence phenotypes have not been published.…”

“…RHDV GI.2 has also been detected as highly virulent in different hare species [138] either as a result of spill-overs from closest rabbit populations or from hare to hare transmission. These findings have highlighted the need for studies into virus cross species infections in lagomorphs [130,132]. Recent detection of RHDV GI.2 and EBHSV GII.1 recombinant viruses [139] highlight the capacity for evolution of the lagoviruses and indicate the importance of continued vigilance in order to protect vulnerable lagomorph species.…”

Frequent intergenotypic recombination between the non-structural and structural genes is a major driver of epidemiological fitness in caliciviruses

“…As surveillance efforts and technologies improved, non-pathogenic GI.3 (RCV-E1) and GI.4 (RCV-A1, RCV-E2) lagoviruses were identified in the 1990s, first in Europe [10][11][12][13] and then in Australia [14] and New Zealand [15]. Non-pathogenic hare lagoviruses (GII.2, GII.3, GII.4, GII.5; HaCV) have also been reported more recently, in 2014 in Europe [16][17][18] and 2019 in Australia [19].…”