L-MEQ gene of non-oncogenic serotypes 1 strains of Marek's Disease virus (MDV1) can suppress transcription activities of the MEQ protein of oncogenic MDV1

Kyung-Soo Chang, PhDa, Kazuhiko Ohashi, PhDa, Sung-Il Lee, PhDa, Ahmed Ibrahim, PhDb, Misao Onuma PhDa

a Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan, b Department of poultry disease, Faculty of Veterinary Medicine, South valley University, Egypt

Strains of Marek's Disease Virus (MDV) are classified into 3 serotypes based on their pathogenesis, and only serotypes 1 strains of MDV (MDV1) are oncogenic to in chickens. Vaccination with non-oncogenic MDV1 can protect chickens from tumor formation by oncogenic MDV1. However, the transformation mechanism by MDV1 and the protection mechanism by vaccines have not been fully understood. One of the candidate oncogenes, MEQ which encodes a bZIP transactivator protein, has been identified in the MDV1 genome, and suggested to play a key role in transformation by MDV1. We have previously found that the L-MEQ gene, in which the 180-bp sequence is inserted into the meq gene, is present in a non-oncogenic MDV1 vaccine strains. To study the function of a gene product of L-meq (L-MEQ), transactivation of L-MEQ was analyzed by dual luciferase assay using a reporter gene under the control of the meq promoter. L-MEQ transactivated the expression of the reporter gene, but this activation was lower compared to MEQ. Furthermore, lower transactivation was observed in cells co-transfected with both meq and L-MEQ than cells transfected only with meq, showing that L-MEQ could be a transrepressor. Replication of oncogenic MDV1 was enhanced in CEF transfected with meq while suppressed in CEF transfected with L-MEQ or both L-meq and meq, compared to untransfected CEF. Thus, L-MEQ can function as a transactivator (or transrepressor), and L-MEQ of the attenuated vaccine strain of MDV1 may contribute, at least in part, to the protection mechanism through the suppression of oncogenic MDV1 replication.

KEY WORDS: Marek's disease virus (MDV), meq, L-meq, transactivator, transrepressor.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Viral Oncogenesis.