Variant Rabbit Hemorrhagic Disease Virus in Young Rabbits, Spain

Kevin P. Dalton, Inés Nicieza, Ana Balseiro, María A. Muguerza, Joan M. Rosell, Rosa Casais, Ángel L. Álvarez, and Francisco Parra

Author affiliations: Universidad de Oviedo Instituto Universitario de Biotecnología de Asturias, Oviedo, Spain (K.P. Dalton, I. Nicieza, A.L. Álvarez, F. Parra); Centro de Biotecnología Animal (SERIDA), Gijón, Spain (A. Balseiro, R. Casais); INTIA División ITG, Navarra, Spain (M.A. Muguerza); and Cunivet Service, Tarragona, Spain (J.M. Rosell)

Abstract

Outbreaks of rabbit hemorrhagic disease have occurred recently in young rabbits on farms on the Iberian Peninsula where rabbits were previously vaccinated. Investigation identified a rabbit hemorrhagic disease virus variant genetically related to apathogenic rabbit caliciviruses. Improved antivirus strategies are needed to slow the spread of this pathogen.

Rabbit hemorrhagic disease (RHD) is rapidly fatal, with mortality rates of 70%–100% in adult rabbits (1); young rabbits (kits) are unaffected or subclinically infected (1,2). This difference in disease susceptibility is poorly understood, but it may be due to changes in tissue-specific receptors that occur as young rabbits develop to adulthood (3).
RHD is caused by Rabbit hemorrhagic disease virus (RHDV; genus Lagovirus, family Caliciviridae) (4), a virus with a positive-sense, single-stranded RNA genome of 7.4 kb. The single serotype of RHDV is divided into 2 subtypes, classic RHDV and RHDVa. Effective inactivated vaccines prepared from liver extracts of rabbits experimentally infected with classic RHDV strains are used as a prophylactic and postoutbreak strategy to combat disease (1).
RHDV is not cultivatable in cell culture; therefore, detection of virus genome, virions, and anti-RHDV antibodies and experimental infection of rabbits are required for diagnosis and virus characterization (1). Sequence regions of the major capsid protein viral protein (VP) 1 are used to type and classify strains.
The identification of rabbit caliciviruses (RCVs) (5,6), nonpathogenic viruses antigenetically similar to RHDV, and recent descriptions of a pathogenic RCV (7), an RHDV variant grouping with RCV viruses in phylogenetic analysis (8), and nonpathogenic RHDV (9) raise questions about the origins, classification, and nomenclature of these viruses. On the Iberian Peninsula, RHDVa or pathogenic or nonpathogenic RCV isolates had not been reported (10). We report the results of an investigation of outbreaks of RHD among young rabbits on farms on the Iberian Peninsula where rabbits were previously vaccinated for RHDV.