Temporal phase-resolved transcriptomics reveals host determinants of Marek’s disease virus reactivation in transformed chicken T cells

In contrast, both lines converged on a highly conserved late-lytic transcriptional program during Lo-to-DP transitions, sharing 118 viral transcripts, dominated by structural and assembly-associated genes. Among the host transcriptional responses, the Line 82 exhibited activation of TP53-associated stress signaling, chromatin remodeling factors, RNA biogenesis pathways, consistent with a permissive cellular state. In contrast, Line 62 displayed enhanced inflammatory, metabolic and proteostasis-associated signatures, suggesting a restrictive environment that limits early viral induction.

Integrated pathway analysis revealed coordinated remodeling of cytoskeletal trafficking, RNA processing, proteostasis, and lipid metabolism during reactivation, while TP53, MTOR, XBP1, NFKB1/RELA, EIF2AK2, DDX58, and STUB1 emerged as candidate host determinants of lytic permissiveness. Collectively, these findings demonstrate that MDV reactivation is a host-gated process in which cellular state governs initiation of the lytic switch, whereas the downstream reproductive replication proceeds through a conserved viral program.