Virulence of Marek's disease virus in Japan is linked to polymorphisms in the

Marek's disease virus (MDV) causes lymphomas and neurological disorders in chickens. Although vaccination largely controls outbreaks, highly virulent strains continue to emerge. The major MDV-encoded oncoprotein is Meq, functions as a transcription factor. Amino acid polymorphisms in Meq have been reported to influence virulence. Despite routine vaccination, MD still occurs sporadically in Japan. Japanese isolates harbour characteristic Meq polymorphisms, but their impact on MDV virulence remains unclear. We investigated the transcriptional regulation by Meq from Japanese isolates and evaluated the pathogenicity of recombinant MDV (rMDV) encoding Meq from the Japanese isolate Nr-c1. Nr-c1-Meq exhibited reduced transrepression and transactivation on viral gene promoters. An rMDV encoding Nr-c1-Meq (vNr-c1-Meq) induced lower mortality and tumourigenicity than an rMDV encoding Meq from the parental very virulent RB-1B strain (vRB-1B). vNr-c1-Meq did not cause visceral tumours or neurological disorders but resulted in distinct clinical signs, including open-mouth breathing. In lymphoid tissues from vNr-c1-Meq-infected chickens, a lower proportion of CD4