Rabbit hemorrhagic disease virus 2, 2010-2023: a review of global detections and affected species

Abstract

Rabbit hemorrhagic disease virus 2/genotype GI.2 (RHDV2/GI.2; Caliciviridae, Lagovirus) causes a highly contagious disease with hepatic necrosis and disseminated intravascular coagulation in several Leporidae species. RHDV2 was first detected in European rabbits (Oryctolagus cuniculus) in France in 2010 and has since spread widely. We gather here data on viral detections reported in various countries and affected species, and discuss pathology, genetic differences, and novel diagnostic aspects. RHDV2 has been detected almost globally, with cases reported in Europe, Africa, Oceania, Asia, and North America as of 2023. Since 2020, large scale outbreaks have occurred in the United States and Mexico and, at the same time, cases have been reported for the first time in previously unaffected countries, such as China, Japan, Singapore, and South Africa, among others. Detections have been notified in domestic and wild European rabbits, hares and jackrabbits (Lepus spp.), several species of cottontail and brush rabbits (Sylvilagus spp.), pygmy rabbits (Brachylagus idahoensis), and red rock rabbits (Pronolagus spp.). RHDV2 has also been detected in a few non-lagomorph species. Detection of RHDV2 causing RHD in Sylvilagus spp. and Leporidae species other than those in the genera Oryctolagus and Lepus is very novel. The global spread of this fast-evolving RNA virus into previously unexploited geographic areas increases the likelihood of host range expansion as new species are exposed; animals may also be infected by nonpathogenic caliciviruses that are disseminated by almost all species, and with which genetic recombination may occur.

Keywords: GI.2; Lagovirus europaeus; Sylvilagus; cottontails; hares; jackrabbits; rabbit hemorrhagic disease; rabbit hemorrhagic disease virus 2; rabbits.

Figure 1.

The order Lagomorpha with genera in families Ochotonidae (pikas) and Leporidae (leporids). Adapted from reference 2 and updated per the International Union for Conservation of Nature–Species Survival Commission, Lagomorph Specialist Group.

Figure 2.

Organization of the Lagovirus genus based on vp60 sequences. Genotypes are established based on genetic differences of >15%. Variants are established based on genetic differences of >6%. EBHSV = European brown hare syndrome virus; HaCV = hare calicivirus (nonpathogenic); RCV = rabbit calicivirus (nonpathogenic); RHDV = rabbit hemorrhagic disease virus.

Figure 3.

World map of rabbit hemorrhagic disease virus 2 detections reported between 2010 and 2023 in different countries (solid lines) and islands (dashed lines). Countries and islands with reported detections are in orange; earlier detections are darker, and the latest detections are lighter. Countries with no reported detections are in gray. References: Algeria, Australia, Austria, Azores, Belgium, Benin, Berlengas, Canada, Canary Islands, China, Cuba, Denmark, Egypt, Finland, France, Germany, Ghana, Gotland, Hawaii, Iceland, Ireland, Isle of Man, Israel, Italy, Ivory Coast (RHDV2 was most likely present at least since 2016), Japan, Luxembourg (RHDV2 was most likely present at least since 2015–2017), Madeira, Malta, Mexico, Morocco, Netherlands, New Zealand (RHDV2 was most likely present at least since 2017), Nigeria, Norway, Poland, Portugal, Sardinia, Senegal, Sicily, Singapore, Skokholm, South Africa, Spain, Sweden, Switzerland, Tasmania, Tunisia, United Kingdom, United States. Map developed using Bing technology and adapted.

Figures 4–9.

Gross lesions of rabbit hemorrhagic disease virus 2 infection. Figure 4. Desert cottontail rabbit with blood around the nares. Figure 5. Black-tailed jackrabbit with pulmonary and serosal congestion and hemorrhages, and blood in abdominal cavity. Photo courtesy of Dr. Akinyi Nyaoke, UC Davis. Figures 6–9. Domestic rabbits. Figure 6. Diffuse hepatic pallor and reddening of the capsule with enhanced reticular pattern. Figure 7. Cut section of liver with pallor and reticular pattern. Figure 8. Pulmonary hemorrhages and congestion. Tracheal congestion and foam in the lumen. Figure 9. Marked splenomegaly and mild hepatic pallor.

Figures 10–13.

Microscopic lesions of rabbit hemorrhagic disease virus 2 infection. H&E. Figure 10. Liver from a riparian brush rabbit, with hepatic necrosis, disorganization of hepatocyte cords, hypereosinophilia, pyknosis, karyorrhexis, and hemorrhage. Inset: positive pan-lagovirus immunohistochemistry. Case kindly donated by Dr Peter Chu, UC Davis. Figures 11–13. Domestic rabbits. Figure 11. Lymphoid depletion of follicles in the white pulp of the spleen, and red pulp necrosis with seams of hyaline eosinophilic material. Figure 12. Fibrin thrombi in 2 pulmonary vessels (arrowheads). Figure 13. Fibrin thrombi (arrowheads) in glomerular capillaries.