A Moving Target: The Evolution of Marek's Disease Virus (MDV) Field Strains

Marek's disease (MD) is a malignant T-cell lymphoma of chickens caused by a highly-transmissible alphaherpesvirus called Marek's disease virus (MDV). Originally, this pathogen caused paralysis and nerve inflammation in older chickens (laying hens, breeders), but since the 1960s, field strains of MDV have evolved that rapidly cause T-cell lymphomas in as little as two to three weeks post-infection. MD has been controlled worldwide through the use of vaccines (derived from non-oncogenic, related herpesviruses of chickens and turkeys, or from attenuated MDV strains). These vaccines, however, do not prevent super-infection of chickens with MDV field strains and have apparently served as a selection pressure for increased virulence. A main focus of our research (and this presentation) is on the genetic mutations observed in MDV strains of higher virulence and what implications they have on the selection pressures mediated by vaccines. One prime candidate gene associated with increases MDV virulence is meq, a gene encoding a basic-leucine zipper (bZIP) protein (Meq) capable of forming heterodimers with several cellular bZIP proteins, including cJun. As bZIP proteins are downstream of numerous stress, survival, proliferation and immune response pathways, mutations within a single bZIP protein could have pleiotropic effects on both cellular and viral genome expression. This presentation will focus on the different forms of the Meq protein expressed during infection in vivo, the interaction partners of these proteins, the mutations observed in field strains worldwide, and what these mutations could be contributing to the evolution of MDV virulence in the field.