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Title: Expression of Marek's disease virus oncoprotein Meq during infection in the natural host

item TAI, S H SHELDON - Simon Fraser University
item Hearn, Cari
item UMTHONG, SUDAWAPEE - Michigan State University
item AGAFITEI, OLGA - Simon Fraser University
item Cheng, Hans
item Dunn, John
item NIIKURA, MASAHIRO - Simon Fraser University

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/18/2017
Publication Date: 2/1/2017
Publication URL:
Citation: Tai, S., Hearn, C.J., Umthong, S., Agafitei, O., Cheng, H.H., Dunn, J.R., Niikura, M. 2017. Expression of Marek's disease virus oncoprotein Meq during infection in the natural host. Virology. 503:103-113. doi:10.1016/j.virol.2017.01.011.

Interpretive Summary: Marek’s disease is an economically important virally-induced lymphoproliferative disease of chickens, which causes over $2 billion in losses worldwide each year. Understanding how Marek’s disease virus induces tumors is crucial for future control. In this study, using a novel method to follow the expression of Meq, which is the viral oncogene, we find that Meq expression is not necessary for the viral to go latent, a mechanism to avoid the host immune system. These results shed light on the mechanism of MDV-induced transformation, which may lead to better vaccinal control.

Technical Abstract: Marek's disease virus (MDV, Gallid herpesvirus 2) causes a lymphoproliferative disease known as Marek's disease (MD), which is unique among alphaherpesviruses as the viral genome encodes an oncoprotein, Meq. Previous studies, using cultured fibroblasts and MDV-transformed lymphoblastoid cell lines, have shown that Meq is consistently expressed in lytically infected and latently infected transformed cells. However, the dynamics of Meq expression in vivo during the course of infection and its temporal role in MD pathogenesis remains unclear. By fusing a "self-cleaving" GFP to Meq, we generated a recombinant MDV that expresses green fluorescent protein (GFP) simultaneously with Meq, which provides an easily-measured marker for Meq expression. Addition of this GFP tag does not impact viral in vitro growth kinetics or in vivo pathogenicity compared to the parental bacterial artificial chromosome-derived Md5 strain. Using this recombinant MDV to infect chickens, we find Meq expression was minimal during the early lytic phase in peripheral blood mononuclear cells (PMBC) and lymphocytes isolated from thymus, spleen, and bursa of Fabricius. In PBMC, the percentage of Meq-expressing cells dramatically increased in the early latent phase but decreased later. Moreover, based on qPCR to monitor MDV load, we find two populations of latently infected CD4+ T cells; one that expresses Meq and another that does not. These findings provide the first insight into the temporal relationship between Meq expression and MD progression, and new clues to refine the current MD pathogenesis model.