Abstract
In the early 1980s, a highly contagious viral hemorrhagic fever in rabbits (Oryctolagus cuniculus) emerged, causing a very high rate of mortality in these animals. Since the initial occurrence of the rabbit hemorrhagic disease virus (RHDV), several hundred million rabbits have died after infection. The emergence of genetically-different virus variants (RHDV GI.1 and GI.2) indicated the very high variability of RHDV. Moreover, with these variants, the host range broadened to hare species (Lepus). The circulation of RHDV genotypes displays different virulences and a limited induction of cross-protective immunity. Interestingly, juvenile rabbits (<9 weeks of age) with an immature immune system display a general resistance to RHDV GI.1, and a limited resistance to RHDV GI.2 strains, whereas less than 3% of adult rabbits survive an infection by either RHDV GI.1. or GI.2. Several not-yet fully understood phenomena characterize the RHD. A very low infection dose followed by an extremely rapid viral replication could be simplified to the induction of a disseminated intravascular coagulopathy (DIC), a severe loss of lymphocytes—especially T-cells—and death within 36 to 72 h post infection. On the other hand, in animals surviving the infection or after vaccination, very high titers of RHDV-neutralizing antibodies were induced. Several studies have been conducted in order to deepen the knowledge about the virus’ genetics, epidemiology, RHDV-induced pathology, and the anti-RHDV immune responses of rabbits in order to understand the phenomenon of the juvenile resistance to this virus. Moreover, several approaches have been used to produce efficient vaccines in order to prevent an infection with RHDV. In this review, we discuss the current knowledge about anti-RHDV resistance and immunity, RHDV vaccination, and the further need to establish rationally-based RHDV vaccines.
Highlights
Interactions between pathogens and their hosts certainly play a key role in the development of biological diversity, following an ever-ongoing ‘arms race’ in which pathogen virulence and host resistance mechanisms co-evolve with each other, leading to a dynamic equilibrium
The regulation towards T-effector cell-mediated immune mechanisms in juvenile rabbits might be similar to rare cases of adult rabbits surviving the rabbit hemorrhagic disease virus (RHDV) infection, in which a less severe T-cell loss is seen compared to moribund rabbits [102,118]
Protective immune mechanisms preventing severe clinical processes are mostly developed in juvenile rabbits, but rarely in adults, The more robust innate immune response in juvenile rabbits was characterized as one reason for the RHDV resistance in a transcriptome analysis-based study [127]
Summary
Interactions between (viral) pathogens and their hosts certainly play a key role in the development of biological diversity, following an ever-ongoing ‘arms race’ in which pathogen virulence and host resistance mechanisms co-evolve with each other, leading to a dynamic equilibrium. The pathology of RHD is similar, and is characterized by a severe clinical course and high mortality rates from 90 to 100% as a result of progressive multi-organ failure resulting from the development of DIC syndrome [38]. One phenomenon of RHD is the resistance of juvenile rabbits against a RHDV infection until the age of 4 weeks (GI. strains) and 9 weeks (GI. strains), respectively, in contrast to the about 3% of adult rabbits which survive after more or less severe clinical symptoms [6]. An in-depth characterization of the humoral and cellular immune mechanisms after RHDV infection comparing the different regulation in juvenile and adult rabbits could provide the knowledge base for rational anti-RHDV vaccine development
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