Transcriptional and Metabolomic Profiling Reveals Potential Molecular Mechanisms for Host Response to Oncogenic Marek’s Disease Virus Infection in Wenchang Chickens

Marek’s disease (MD) caused by Marek’s disease virus (MDV), poses a serious threat to the poultry industry worldwide by inducing neurological disease and malignant lymphoma in infected chickens. Moreover, the underlying mechanisms how the host reacts to MDV infection and tumorigenesis still remain exclusive. We compared the transcriptomic and metabolomic responses of the heart tissue of Wenchang chicken, an indigenous species of China, using RNA-sequencing and untargeted metabolomics technology to gain an understanding of the molecular mechanisms underlying the host response to MDV infection. A total of 2,470 and 2,666 genes showed significant up- and down-regulation between infected and uninfected chickens. KEGG pathway enrichment results revealed different transcriptional patterns between up- and down-regulated genes in response to MDV infection, with the up-regulated genes mostly enriched in pathways related to immunity and the down-regulated genes enriched in metabolism-related pathways. A total of 433 differentially expressed metabolites were identified between the infected and uninfected groups, and only caffeine metabolism pathway was nearly significantly enriched (p = 0.067). Mapping of differentially expressed genes and metabolites to KEGG enzyme database revealed that L_Kynurenine pairing with KYNU, KMO, KYAT3 and AADAT was the most representative among these top corresponding relationships. Our results provided a quantitative snapshot of MDV infection changes in host transcription and metabolism, and we hypothesized that the host may actively respond to MDV infection and tumor progression by suppressing cellular metabolism to induce a stronger immune response.