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ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Avian Disease and Oncology Research » Research » Publications at this Location » Publication #300730

Title: Temporal kinetics of Marek's disease herpesvirus: integration occurs early after infection in both B and T cells

Author
item ROBINSON, CHARMAINE - University Of California
item Cheng, Hans
item DELANY, MARY - University Of California

Submitted to: Cytogenetics and Genome Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/18/2014
Publication Date: 11/8/2014
Publication URL: http://handle.nal.usda.gov/10113/60307
Citation: Robinson, C.M., Cheng, H.H., Delany, M.E. 2014. Temporal kinetics of Marek's disease herpesvirus: integration occurs early after infection in both B and T cells. Cytogenetics and Genome Research. 144(2):142-154. doi: 10.1159/000368379.

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 a-herpesvirus that induces Marek's disease characterized by fatal lymphomas in chickens. Here, we explored the timing during pathogenesis when the virus integrates into the host genome, the cell type involved, the role of viral integration on cellular transformation, and tumor clonality. Three immune organs of chicken (thymus, bursa, and spleen) were extracted following infection with either an oncogenic or a non-oncogenic strain of MDV. Using molecular cytogenetics, cells were investigated for viral integration at key time points throughout pathogenesis. Integration profiling of tumors (early to late stage) was conducted. Virus integration was widespread in B and T lymphocytes based on their abundance in bursa and thymus, respectively. Viral replication was detected early after infection as was viral integration into the host genome. Integration is a natural part of the MDV herpesvirus life cycle. In addition, our data using a non-oncogenic virus establish that although integration is a hallmark of tumor cell populations, integration alone is not sufficient for cellular transformation. Our results provide evidence for progression of lineage clonality within tumors. Understanding the features of integration provides insight into the mechanisms of herpesvirus pathology which could lead to disease mitigation strategies.