Highly virulent RHDV2 strains: a risk for our pet rabbits!
Introduction
Rabbit Haemorrhagic Disease is a viral lethal disease that affects rabbits. Its outbreaks have devastating consequences in the rabbit populations. Among its genotypes, the RHDV2 - also known as GI.2 - has distinguished itself through its broader host range, ability to infect young rabbits, capacity for rapid mutation and recombination, and increasing virulence. Since its first detection in France in 2010, RHDV2 has spread across Europe, America, and parts of Oceania and Asia, fundamentally reshaping the RHD epidemiology.
Unlike classical RHDV (GI.1), which primarily affected adult rabbits (Oryctolagus cuniculus), RHDV2 has been found to infect rabbits of all ages, as well as other lagomorph species, including various hares (Lepus spp.) and cottontails (Sylvilagus spp.). Its capacity to cross species barriers and adapt rapidly has made RHDV2 a formidable pathogen in both wild and domestic environments.
RHDV belongs to the Caliciviridae family and is a non-enveloped, single-stranded, positive-sense RNA virus. Its high mutation rate and genetic plasticity are characteristic of RNA viruses, enabling the frequent emergence of novel variants with enhanced pathogenic potential. The virus primarily targets the liver, causing massive hepatic necrosis and widespread hemorrhages, often leading to disseminated intravascular coagulation (DIC) and multi-organ failure within 24–72 hours of infection.1
Highly Virulent RHDV2 Strains
Initial reports described RHDV2 as having relatively lower mortality compared to classical RHDV, especially in adult rabbits. However, several studies demonstrated a significant increase in the virulence of RHDV2 strains , with some reaching near 100% mortality2,3. This contrasts with the firsts RHDV2 isolates that characterized the virus as moderately pathogenic1. While some strains exhibit attenuated pathogenicity, others are more lethal than their parental strains.
Several factors can contribute to increase the virulence of RHDV 4,5,6,7:
- Genetic recombination: Recombination between different strains of RHDV has led to the emergence of highly virulent variants. These recombination events can result in new viral strains with enhanced pathogenicity.
- High mutation rates: The high mutation rate of RHDV, as RNA virus, allows it to adapt quickly to new environments and hosts. This rapid evolution can lead to the development of more virulent strains.
- Host-virus co-evolution: The interaction between RHDV and the high reproduction cycle of its host (rabbits and hares) plays a crucial role in the evolution of virulence. As the virus adapts to the host's immune system, it can become more efficient at evading immune responses and causing severe disease.
Risks for pet rabbits
Pet rabbits, like dwarf or other domestic rabbits, are susceptible to highly virulent RHDVs strains. The risks for pet rabbits include:
- High mortality rate: highly virulent RHDV2 strains can cause death in 80-100% of infected rabbits, often within 1-3 days of symptom onset. 8,9
- High resistance of the virus in the environment: it can survive in animal tissues for at least 3 months in the field or 1 month when it is exposed directly to environmental conditions.10
- Transmission: The virus spreads through direct contact with infected rabbits or their secretions, as well as through contaminated objects, food, water, and even insects. So, even indoor rabbits without contact with other animals can be infected.11
- Limited surveillance and misdiagnosis: sudden death in unmonitored areas may be wrongly attributed to other causes.
Prevention
Considering the resistance of the virus in the environment, biosecurity measures are essential to prevent transmission within the veterinary center. These measures include isolating sick rabbits, maintaining a clean environment, and controlling vectors, among others.
Given that there is no specific treatment for the disease, only supportive care, and considering the higher virulence of current RHDV2 strains, prevention by vaccination is the only effective tool to protect rabbits. To design the vaccination strategy, we should consider the following factors when choosing the vaccines to administer:
- Protection against multiple RHD strains: Vaccines like YURVAC® RHD provide protection against various strains of RHDV, including highly virulent RHDV2 strains. This broad-spectrum protection is crucial for preventing outbreaks and mortality.8,9
- High immunity: Vaccines that produce a strong serological response, ensuring long-term protection. 9
In conclusion, vaccination protocols should be adapted to the epidemiological situation of each country. Regular vaccinations will help control the spread of RHDV2 by reducing the number of susceptible rabbits.

References
- Lavazza, A.; Capucci, L. Chapter 3.6.2.—Rabbit haemorrhagic disease. In Manual of Diagnostic Tests and Vaccines for Terrestrial Animals 2021; OIE: Paris, France, 2021; pp. 1389–1406.
- Capucci L, Cavadini P, Schiavitto M, Lombardi G, Lavazza A. Increased pathogenicity in rabbit haemorrhagic disease virus type 2 (RHDV2). Vet Rec. 2017;180:426
- Peter Elsworth, Brian D. Cooke, John Kovaliski, Ronald Sinclair, Edward C. Holmes, Tanja Strive. Increased virulence of rabbit haemorrhagic disease virus associated with genetic resistance in wild Australian rabbits (Oryctolagus cuniculus). Vet Sci. 2014 Sept. Vol 464–465, Pag. 415-423. doi.org/10.1016/j.virol.2014.06.037
- Mahar, J.E., Jenckel, M., Huang, N., Smertina, E., Holmes, E.C., Strive, T., et al., 2021. Frequent intergenotypic recombination between the non-structural and structural genes is a major driver of epidemiological fitness in caliciviruses. Virus Evol. 7, veab080. https://doi.org/10.1093/ve/veab080.
- Abrantes, J., Droillard, C., Lopes, A.M. et al. Recombination at the emergence of the pathogenic rabbit haemorrhagic disease virus Lagovirus europaeus/GI.2. Sci Rep 10, 14502 (2020). https://doi.org/10.1038/s41598-020-71303-4
- Patrizia Cavadini, Tiziana Trogu, Roser Velarde, Antonio Lavazza, Lorenzo Capucci. Recombination between non-structural and structural genes as a mechanism of selection in lagoviruses: The evolutionary dead-end of an RHDV2 isolated from European hare. Sci. Direct. Virus Research 339, 199257 (2024). https://doi.org/10.1016/j.virusres.2023.199257
- Abrantes, J., Droillard, C., Lopes, A.M., Lemaitre, E., Lucas, P., Blanchard, Y., et al., 2020a. Recombination at the emergence of the pathogenic rabbit haemorrhagic disease virus Lagovirus europaeus/GI.2. Sci. Rep. 10, 14502–14504. https://doi.org/ 10.1038/s41598-020-71303-4.
- Perozo E, Fontseca M, Nadal G, Montbrau G, Gascon-Torrens S, March R, et al. Efficacy evaluation of YURVAC® RHD against a current highly virulent RHDV2 strain. In: 13th World Rabbit Congress. 2024.
- Perozo E., Fontseca M., Acal L., Gascon S., March R., Sitjà M. YURVAC® RHD vaccine against RHDV and RHDV2. In: Icare Congress. 2024.
- Henning J, Meers J, Davies PR, Morris RS. Survival of rabbit haemorrhagic disease virus (RHDV) in the environment. Epidemiol Infect. 2005 Aug;133(4):719-30. doi: 10.1017/s0950268805003766. PMID: 16050519; PMCID: PMC2870301.
- Pinto FF, Abrantes J, Ferreira PG, Nóbrega M, Marcos R. Case series: Four fatal rabbit hemorrhagic disease virus infections in urban pet rabbits. Front Vet Sci. 2023 Mar 22;10:1144227. doi: 10.3389/fvets.2023.1144227. PMID: 37035809; PMCID: PMC10073570.