Wessel van der Loo

Rabbit haemorrhagic disease virus (RHDV) is a calicivirus of the genus Lagovirus that causes rabbit haemorrhagic disease (RHD) in adult European rabbits (Oryctolagus cuniculus). First described in China in 1984, the virus rapidly spread worldwide and is nowadays considered as endemic in several countries. In Australia and New Zealand where rabbits are pests, RHDV was purposely introduced for rabbit biocontrol. Factors that may have precipitated RHD emergence remain unclear, but non-pathogenic strains seem to pre-date the appearance of the pathogenic strains suggesting a key role for the comprehension of the virus origins. All pathogenic strains are classified within one single serotype, but two subtypes are recognised, RHDV and RHDVa. RHD causes high mortality in both domestic and wild adult animals, with individuals succumbing between 48-72 h post-infection. No other species has been reported to be fatally susceptible to RHD. The disease is characterised by acute necrotising hepatitis, but haemorrhages may also be found in other organs, in particular the lungs, heart, and kidneys due to disseminated intravascular coagulation. Resistance to the disease might be explained in part by genetically determined absence or weak expression of attachment factors, but humoral immunity is also important. Disease control in rabbitries relies mainly on vaccination and biosecurity measures. Such measures are difficult to be implemented in wild populations. More recent research has indicated that RHDV might be used as a molecular tool for therapeutic applications. Although the study of RHDV and RHD has been hampered by the lack of an appropriate cell culture system for the virus, several aspects of the replication, epizootology, epidemiology and evolution have been disclosed. This review provides a broad coverage and description of the current knowledge on the disease and the virus.

Studies using the European rabbit Oryctolagus cuniculus contributed to elucidating numerous fundamental aspects of antibody structure and diversification mechanisms and continue to be valuable for the development and testing of therapeutic humanized polyclonal and monoclonal antibodies. Additionally, during the last two decades, the use of the European rabbit as an animal model has been increasingly extended to many human diseases. This review documents the continuing wide utility of the rabbit as a reliable disease model for development of therapeutics and vaccines and studies of the cellular and molecular mechanisms underlying many human diseases. Examples include syphilis, tuberculosis, HIV-AIDS, acute hepatic failure and diseases caused by noroviruses, ocular herpes, and papillomaviruses. The use of rabbits for vaccine development studies, which began with Louis Pasteur’s rabies vaccine in 1881, continues today with targets that include the potentially blinding HSV-1 virus infection and HIV-AIDS. Additionally, two highly fatal viral diseases, rabbit hemorrhagic disease and myxomatosis, affect the European rabbit and provide unique models to understand co-evolution between a vertebrate host and viral pathogens. Rabbits offer a powerful complement to rodents as a model for studying human immunology, disease pathology, and responses to infectious disease. A review from Pedro Esteves at the University of Porto, Portugal, Rose Mage of the National Institute of Allergy and Infectious Disease, Bethesda, USA and colleagues highlights some of the areas of research where rabbits offer an edge over rats and mice. Rabbits have a particularly sophisticated adaptive immune system, which could provide useful insights into human biology and produce valuable research and clinical reagents. They are also excellent models for studying - infectious diseases such as syphilis and tuberculosis, which produce pathology that closely resembles that of human patients. Rabbit-specific infections such as myxomatosis are giving researchers insights into how pathogens and hosts can shape each other’s evolution.

B lymphocytes capable of generating primary IgM and IgG plaque-forming cells (PFC) responses to burro erythrocytes have surface IgD, as do primary IgM PFC. IgG memroy cells arising after one injection of antigen are divided into two groups, one of which expresses surface IgD while the other has no detectable membrane IgD. PFC generated from the IgG memory cells lacking surface IgD show a higher average avidity than those arising from IgD-positive IgG memory cells, indicating that mature IgG memory cells do not have surface IgD. After more than one injection of antigen, few, if any, IgG memory cells have surface IgD. IgG PFC arising in primary or secondary immune response lack membrane-bound IgD. These data provide the outlines for a B-cell maturation pathway in which IgD marks unprimed and early memory B cells and is lost in mature memory cells. Studies presented here were conducted by isolating IgD+ and IgD- cells with the fluorescence-activated cell sorter and functional testing of the isolated populations in adoptive transfer experiments.

A rabbit of allotype a1a3, b4b5 was hyperimmunized with lyophilized Micrococcus lysodeikticus. Two weeks after the appearance of antibodies of restricted heterogeneity, the serum immunoglobulins of this animal reacted with anti-a1, anti-a2, anti-a3, and anti-b4, anti-b5, and anti-b6 allotype antisera. Control experiments showed that the reaction was specific for the allotypic determinants and that cross-reactions could be excluded. Isolated light chains were shown to contain the b4, b5, and b6 allotypic specificities. Serial bleedings indicated that all six allotypic specificities were present in most bleedings, but occasionally one or more of the allotypic specificities could not be detected.

Abstract A rabbit of allotype a1a3, b4b5 was hyperimmunized with lyophilized Micrococcus lysodeikticus. Two weeks after the appearance of antibodies of restricted heterogeneity, the serum immunoglobulins of this animal reacted with anti-a1, anti-a2, anti-a3, and anti-b4, anti-b5, and anti-b6 allotype antisera. Control experiments showed that the reaction was specific for the allotypic determinants and that cross-reactions could be excluded. Isolated light chains were shown to contain the b4, b5, and b6 allotypic specificities. Serial bleedings indicated that all six allotypic specificities were present in most bleedings, but occasionally one or more of the allotypic specificities could not be detected.