The oncolytic effect of virotherapy derives from the intrinsic capability of the applied virus in selectively infecting and killing
tumor cells. Although oncolytic viruses of various constructions have been shown to efficiently infect and kill
tumor cells in vitro, the efficiency of these viruses to exert the same effect on
tumor cells within
tumor tissues in vivo has not been extensively investigated. Here we report our studies using single-cell
RNA sequencing to comprehensively analyze the gene expression profile of
tumor tissues following herpes simplex virus 2-based
oncolytic virotherapy. Our data revealed the extent and cell types within the tumor microenvironment that could be infected by the virus. Moreover, we observed changes in the expression of cellular genes, including
antiviral genes, in response to
viral infection. One notable gene found to be upregulated significantly in oncolytic virus-infected
tumor cells was Gadd45g, which is desirable for optimal virus replication. These results not only help reveal the precise
infection status of the oncolytic virus in vivo but also provide insight that may lead to the development of new strategies to further enhance the therapeutic efficacy of
oncolytic virotherapy.