Pathogenesis of infection with attenuated Marek's disease virus strains.

Recently, attenuated Marek's disease virus (MDV) became of renewed interest as a component in bi- or polyvalent vaccines. The effect of attenuation on the pathogenesis of infection was investigated. Cloned preparations of the JM-16, BC-1A and RB-1B strains of MDV were attenuated by serial passage in chick kidney cells or chicken embryo fibroblasts. Subclones were obtained from the JM-16 strain at passage (p) 26 (JM-16d) and 50 (JM-16a, b and c). The passage level at which each virus became attenuated was dependent on the virus strain. The highly oncogenic RB-1B strain was still oncogenic after 37 passages, while JM-was already attenuated at p. 27. In ovo infection of high passage JM-16 and RB-1B (p 54 and 55) demonstrated the presence of residual pathogenicity. Attenuated virus failed to induce the early cytolytic infection which is characteristic for the pathogenesis of infection with oncogenic MDV. Low levels of lymphocyte-associated viraemia could be detected after infection with all attenuated viruses except with the subclone JM-16a. This virus was, however, able to induce moderate protection against challenge and antibodies were detectable, suggesting that cells other than lymphocytes became infected. The pathogenesis after in ovo infection with attenuated virus was similar to that after infection of chicks. The in vivo data suggested that attenuation reduced the efficiency of infection of, or virus replication in, lymphocytes. A markedly reduced ability to establish in vitro infection of lymphocytes by exposure to heavily infected lymphocytes was observed, and this supports this hypothesis. The altered characteristic of attenuated virus to infect lymphocytes in vivo or in vitro was not caused by the selection of temperature sensitive or thymidine kinase negative mutants.