# Virulence of Marek’s disease virus in Japan is linked to polymorphisms in the meq oncogene

## TL;DR

This study shows that variations in the Meq protein of Marek’s disease virus in Japan affect how severe the disease is and the symptoms it causes in chickens.

## Contribution

The study identifies how Meq polymorphisms from Japanese isolates alter virulence and clinical outcomes in Marek’s disease.

## Key findings

- Japanese Meq variants showed reduced transrepression and transactivation of viral gene promoters.
- vNr-c1-Meq caused lower mortality and tumourigenicity compared to the highly virulent RB-1B strain.
- Infection with vNr-c1-Meq led to distinct clinical signs and altered immune cell responses in chickens.

## Abstract

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+ T cells, the targets of MDV transformation, and lower viral loads were observed than those in vRB-1B-infected chickens. Histopathological examination revealed increased lymphocyte infiltration in bronchus-associated lymphoid tissues (BALT) in the vNr-c1-Meq group. Additionally, flow cytometric analysis showed elevated γδ T-cell proportions, which positively correlated with IFN-γ expression in vNr-c1-Meq-infected chickens and were linked to BALT hyperplasia. In comparison to the vRB-1B, vNr-c1-Meq infection resulted in attenuated disease progression and altered clinical signs. These findings suggest that Meq polymorphisms not only influence MD virulence but also clinical presentation.