*5.2. Role of Cell Cycle in Resistance of PDAC Cells to VSV*

We have demonstrated that compounds inducing cell cycle arrest in G1/S-phase or S-phase strongly inhibited VSV-∆M51 replication, while G2/M phase arrest dramatically enhanced the replication of VSV-∆M51 in cells with functional antiviral signaling [61]. It was found that G2/M arrest strongly inhibited IFN production and expression of ISGs in response to exogenously added IFN. The replication of IFN-sensitive cytoplasmic viruses can be strongly stimulated during G2/M phase as a result of inhibition of antiviral gene expression, likely due to mitotic inhibition of transcription, a global repression of cellular transcription during G2/M phase. However, G2/M arrest did not stimulate the replication of VSV-∆M51 in cells defective in IFN signaling, and it did not stimulate replication of WT VSV, which is more effective at evading antiviral responses [61]. Together, our study suggests that continuous cell cycle transition, a hallmark of cancer cells, could be another factor of oncoselectivity for many viruses, at it would facilitate viral replication via inhibition of antiviral responses in dividing cancer cells during G2/M phase. It also suggests that slowly dividing PDAC cells could be more resistant to some OVs than faster dividing PDACs.
