Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2004
Publication Date: 4/1/2005
Citation: Gimeno, I.M., Witter, R.L., Hunt, H.D., Reddy, S.M., Lee, L.F., Silva, R.F. 2005. The pp38 gene of Marek's disease virus (MDV) is necessary for cytolytic infection of B cells and maintenance of the transformed state but not for cytolytic infection of the feather follicle epithelium and horizontal spread of MDV. Journal of Virology. 79(7):4545-4549. Interpretive Summary: Marek's disease (MD), a virus-induced cancer-like disease of chickens, is considered as a major disease problem in commercial poultry. Vaccination has dramatically reduced the incidence of the disease, but more virulent viruses are emerging and development of new control strategies is needed. The objective of this research was to characterize the function of the pp38 gene of the Marek's disease virus (MDV) that has been associated with important events in the development of MD, such as replication, reactivation from latency and tumor formation. We have shown that the deletion of the pp38 gene impairs replication in B cells (a class of lymphocytes), which is a critical step in the disease. Pp38 is also necessary for the progression of tumors since deleting this gene results in an increase in apoptosis (programmed cell death) and thereby prevents tumor formation. This important information about the pp38 gene of MDV will help scientists in academia and industry understand MD and eventually lead to better control of the disease
Technical Abstract: Marek's disease virus (MDV) has a unique phosphoprotein, pp38, which is suspected to play an important role in MD pathogenesis. A variety of relevant functions have been associated with pp38: lymphoid tropism, establishing latency and reactivation, maintenance of tumors and immunosuppression. The objective of the present study was to better characterize the biological function of pp38 by the use of a mutant virus (rMd5'pp38) lacking the gene pp38. Our results showed that rMd5'pp38 has lost the ability to replicate cytolytically in B cells but it did not affect cytolytic replication in the feather follicle epithelium and horizontal transmission. The number of latently infected T cells after infection with rMd5'pp38 was much lower than after infection with rMd5. However, T cells latently infected by both rMd5'pp38 and rMd5 showed similar ability to reactivate in cell culture. RMd5'pp38 was able to transform the same cell phenotype as rMd5 (CD4+ CD8- MATSA+ meq+) but the development of tumors occurred at much lower frequency than after infection with rMd5, in part because lymphoproliferative lesions induced by rMd5'pp38 underwent apoptosis and did not progress to gross tumors. Thus, this work shows that the gene pp38 is necessary to establish cytolytic infection in B cells, to produce an adequate level of latently infected T cells, and to maintain the transformed status in vivo.