Optimization of oncolytic effect of Newcastle disease virus Clone30 by selecting sensitive tumor host and constructing more oncolytic viruses

The direct oncolytic effect of Newcastle disease virus (NDV) depends on the following two aspects: the susceptibility of cancer cells to virus infection and the ability of virus itself to lyse cancer cells. First, we investigate the susceptibility of cancer cells to NDV infection, HepG2, MDA-MB-231, and SH-SY5Y cells were susceptible, A549, MCF7, and LoVo cells were less susceptible. To investigate the molecular mechanism responsible for cancer cell susceptibility, transcriptome sequencing was carried out. We found that the levels of alpha-sialic acid acyltransferase were upregulated in MDA-MB-231 cells compared with MCF7 cells, and the interferon was downregulated. Second, to optimize the oncolytic capacity of the wild-type rClone30, a series of chimeric viruses rClone30-Anh(HN), rClone30-Anh(F), and rClone30-Anh(HN-F) were constructed by exchanging the HN gene, F gene or both of non-lytic rClone30 strain with lytic strain Anhinga. rClone30-Anh(F) and rClone30-Anh(HN-F) enhanced the oncolytic effect of the rClone30, and this enhancement is more obvious in the susceptible cells. The oncolytic mechanism of rClone30-Anh(F) was analyzed by transcriptome analyses, in comparison with rClone30, rClone30-Anh(F) upregulated the expression of ATG5, Beclin 1, and MAP1LC3B, thus activating autophagy and promoting the production of syncytia. In conclusion, our study provides a strategy to enhance the oncolytic effect of rClone30.

Automated summary

The study investigates the direct oncolytic effect of Newcastle disease virus (NDV) on cancer cells, focusing on susceptibility of cancer cells to virus infection and enhancing virus's ability to lyse cancer cells. The research identified susceptible cancer cells and optimized a wild-type virus to enhance its oncolytic effect, providing a strategy for improving rClone30's oncolytic capacity. The findings highlight that certain cancer cells are more susceptible to infection and enhancing the virus strain can significantly boost the oncolytic effect, especially in susceptible cells.