Abstract

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.

Highlights

  • Rabbit haemorrhagic disease (RHD) is a viral disease of the European rabbit (Oryctolagus cuniculus) that primarily affects the liver [1]

  • In this study, clinical signs, disease and case fatality rate caused by the Australian strain of L. europaeus GI.2 closely mimicked that of classic RHD in adult rabbits caused by L. europaeus GI.1 strains [1]

  • It is not possible to predict whether this animal would have survived or succumbed to subacute RHD, but this variation in disease progression and mortality rate among animals is consistent with that seen in classic RHD caused by GI.1 and differs from the longer disease course and lower case fatality rates described for early strains of GI.2 [2]

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Summary

Introduction

Rabbit haemorrhagic disease (RHD) is a viral disease of the European rabbit (Oryctolagus cuniculus) that primarily affects the liver [1]. The causative agents, currently known as rabbit haemorrhagic disease virus (RHDV), the antigenic variant (RHDVa), and the recently described RHDV2 or RHDVb, are lagoviruses within the Family Caliciviridae [1, 2]. Within a proposed new classification system [3], all lagoviruses are reclassified into a single species, Lagovirus europaeus, and the causative viruses. First described in domestic rabbits in China in 1984, RHD was detected in Europe in 1986 and has been documented at some point on every continent except Antarctica [1]. In Australia and New Zealand, RHD is used intentionally for biocontrol of invasive, introduced European rabbits. Until 2010, the disease was almost exclusively confined to wild and domestic European rabbits and was caused by viruses newly classified as genotype 1 of the L. europaeus GI group (i.e. L_europaeus GI.1 [3]), known as RHDV and RHDVa (Table 1). L. europaeus GI. is further subdivided into variants denoted by lower case letters [3] (Table 1)

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