|Miller, Marsha - CITY OF HOPE NATL MED CTR|
|Gimeno, Isabel - UNIVERSIDAD COMPLUTENSE|
|Parcells, Mark - UNIVERSITY OF ARKANSAS|
Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 18, 2000
Publication Date: N/A
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 very little is known about the viral products involved in the induction of disease. The objective of this research was to characterize the mechanism by which MD virus (MDV) influence the immune response of the host. We have identified and characterized a process by which MDV inhibits the production of certain proteins necessary for mounting an effective immune response and therefore promote formation of tumors in infected chickens. The information obtained from this research is of great interest to scientists in industry and academia as it will aid in developing the new generation of vaccine viruses that lack the ability to inhibit the host immune system.
Technical Abstract: Infection of chicken cells with the Marek's disease virus (MDV) interferes with expression of the major histocompatibility complex (MHC or B complex) class I (BF) glycoproteins. Active, but not latent, MDV infection effectively blocks cell surface expression of BF glycoproteins. This block in BF surface expression occurs after infection of chicken fibro- blast cells (OU2) with MDV serotypes 1(Md11), 2(SB1) and 3(HVT). The MDV T cell tumor lines, MDCC-UA04 and MDCC-MSB1, express normal levels of BF glycoproteins, however nearly complete loss of cell surface BF is observed upon virus reactivation with 5-bromo-2'-deoxyuridine (BUdR). The recombinant virus (RB1BUS2gfp) transforming the MDCC-UA04 cell line expresses green fluorescent protein (GFP) during the immediate early phase of viral gene expression. Of the UA04 cells induced to express the immediate early GFP, approximately 60% have reduced levels of BF expression. All of the reactivated UA04 and MSB1 tumor cells expressing the major early viral protein pp38 display reduced levels of BF. Thus, BF down regulation begins in the immediate early and is complete by the early phase of viral gene expression. Although the cell surface BF glycoproteins are severely down regulated, the intra-cellular pool of BF is abundant showing the mechanism is not the result of transcription or translational regulation. Histochemical analysis of MDV induced tumor cells shows this inhibition of cell surface BF expression is observed in-vivo and suggests it may play a role in the pathogenicity of MDV.