Differential attenuation of the induction by Marek's disease virus of transient paralysis and persistent neurological disease: A model for pathogenesis studies

Abstract

Since different biological characteristics of Marek's disease virus (MDV) are attenuated at different passage levels in cell culture, an analysis of attenuation times provides, in theory, a model for establishing the presence or absence of relationships between characteristics, thus providing a basis to link them to genetic changes in the causative virus. We have used this model to better understand the pathogenesis of the central nervous system infection as well as to evaluate the relationship of clinical neurological disease to various other parameters of MDV infection. Inoculation of 15 2 7 crossbred chickens with strain 648A of very virulent plus MDV at different passage levels (between 10 and 100) showed that two neurological syndromes (transient paralysis (TP) and persistent neurological disease), were attenuated at different passage levels. While strain 648A lost the ability to induce TP between 30 and 40 passages in chicken embryo fibroblast cultures, an event closely related with all parameters of MDV infection involving viral replication (early cytolytic infection in lymphoid organs and viral replication in the feather follicle epithelium), the ability to induce persistent neurological disease was lost between 80 and 90 passages in chicken embryo fibroblasts, coincident with the loss of neoplastic lesions in peripheral nerves and other visceral organs. These data strongly suggest that transient paralysis and persistent neurological disease are unrelated and differently regulated. Moreover, comparison of brain changes induced by strain 648A at passage level 30 (TP) and at passage level 40 (no TP) also contributed to a better understanding of which brain alterations are associated with the onset of TP. The use of viruses at different passage levels with varying degrees of attenuation is presented as a useful tool for studying pathogenesis of MDV infection.