Location: Avian Disease and Oncology Laboratory
Title: Marek’s disease virus and chicken host genome interactions Authors
|Robinson, Charmaine -|
|Delany, Mary -|
Submitted to: PLoS Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 18, 2014
Publication Date: N/A
Interpretive Summary: Marek’s disease virus (MDV) is a very important pathogen in chickens that costs the worldwide poultry industry $1-2 billion annually. A greater understanding how the virus promotes T cell tumors should provide opportunities for improved disease control. In this submission, we find that the virus integrates into the chicken genome early and rapid as part of its natural life cycle. Also a non-oncogenic viral strain can also integrate in the chicken genome, which indicates that integration is not sufficient for tumor formation and challenges the current presumption that viral integration only occurs in tumors. This information provides a strong basis for future studies on the evolution of more virulent MDV field strains and the development of more effective vaccines.
Technical Abstract: Marek’s disease virus (MDV) is an oncogenic avian alphaherpesvirus that induces Marek’s disease (MD), which is characterized by fatal lymphomas in chickens. Like a few other pathogenic viruses, MDV has been shown to integrate into the host genome. Using this unique in vivo model system, we explored the timing during disease progression when integration is first observed, the cell type involved, and the role of viral integration on cellular transformation. Three major immune organs of chicken, thymus, bursa of Fabricius and spleen, were harvested following infection with either an oncogenic strain or a non-oncogenic strain of MDV. Individual cells were investigated for viral integration at several key time points throughout pathogenesis using molecular cytogenetics. MDV integration was found to be a widespread phenomenon, presumed to be ubiquitous across B and T lymphocytes based on their abundance in bursa and thymus, respectively. Surprisingly, viral replication was prevalent and detected early post-infection as was viral integration into the host genome, concomitant with the early viral lytic and latent infection periods. Our data using a non-oncogenic Meq-deleted virus establishes that for MDV, although integration is a hallmark of tumor cell populations, integration alone is not sufficient for cellular transformation. Understanding the role integration plays in achieving latency, pathogenesis, and tumorigenesis provides valuable insights on the mechanisms of herpesvirus pathology.