Detailed molecular investigation of Marek’s disease virus circulating in organised poultry farms in India revealed emergence of highly virulent MDV causing varied tissue tropism

1. The current study analysed Marek's Disease virus (MDV) strains, genome characteristics and associated pathology, with reference to the central nervous system, in naturally occurring field cases across India.2. A total of 179 birds, aged less than 18 weeks, with visible visceral tumours in any of the organs were collected from major poultry areas of India. The source flocks were all vaccinated against MDV. Gross, cytological and histopathological examinations were conducted, alongside PCR for detecting MDV in lymphomatous tissues and the brain. The genetic characterisation and phylogenetic analyses of <i>meq</i> gene were conducted.3. The liver and spleen were affected in all cases, followed by the proventriculus, kidneys, heart, lungs, pancreas and sciatic nerves. Histopathologically, infiltration of pleomorphic lymphocytes was observed in affected organs, including the brain.4. All the cases were PCR-positive for the MDV genome, including four cases involving the brain. Four representative full-length sequences of the MDV <i>meq</i> gene from the brain exhibited amino acid substitutions (A-E-Y-R-V-C-P-P-T-P-L) at key positions, characteristic of virulent MDV strains.5. The findings indicated the circulation of virulent strains among MDV samples from India, based on sequence analysis and pathology involving the brain. Field isolates from the sampled locations were virulent forms of MDV and under positive selection, leading to varied tissue tropism, such as brain affinity, which has been previously reported in virulent MDV.6. The study highlighted the emergence of neurotropic, virulent MDV strains in India, underscoring the need for vigilant surveillance and revised vaccination strategies. Brain involvement in naturally occurring field cases suggests expanding tissue tropism with potential implications for diagnosis and disease control.