Canine Distemper Virus-Induced Transcriptional Modulation of Canine Histiocytic Sarcoma Cells in an In Vitro Model of Tumour Zones.

Canine distemper virus (Onderstepoort strain; CDVOnd) exhibits potential oncolytic properties. However, the detailed molecular mechanisms remain undetermined so far. This study investigated the influence of a CDVOnd infection and various culture conditions on gene expression patterns in canine histiocytic sarcoma (DH82) cells at different time points simulating different zones within a solid tumour. Persistently CDVOnd-infected DH82 cells and non-infected controls were cultured under standard conditions, 1% hypoxia, and starvation. Cells were analysed on day 1 (short-term) and day 3 (prolonged exposure) using proliferation assays and RNA sequencing. The number of infected cells significantly decreased under altered compared to control conditions and decreased after prolonged compared to short-term exposure. Enrichment analysis revealed that persistent CDV infection, compared to non-infected controls, upregulated genes associated with immune processes and downregulated tissue developmental pathways, including angiogenesis across all conditions and time points. Compared to infected cells maintained under control conditions, hypoxia and starvation induced distinct, condition-dependent transcriptomic responses regardless of exposure duration. Hypoxia led to suppression of immune-related processes and promoted angiogenesis while starvation resulted in an opposite pattern. This suggests that CDV infection induces transcriptomic changes across all zones suggesting anti-tumour effects, while microenvironmental conditions might affect the efficacy of CDV-based virotherapy.