Vaccinia virus Tiantan strain blocks host antiviral innate immunity and programmed cell death by disrupting gene expression

The vaccinia virus Tiantan(VTT)is widely utilized as a smallpox vaccine in China and holds significant impor-tance in the prevention of diseases stemming from poxvirus infections.Nevertheless,few studies have investi-gated the influence of VTT infection on host gene expression.In this study,we constructed time series transcriptomic profiles of HeLa cells infected with both VTT and western reserve(WR)strains.We observed similar patterns of viral gene expression,while the expression levels of host genes varied between the two strains.There was an immediate and significant repression of host gene expression,particularly in genes asso-ciated with oxidative phosphorylation.Conversely,genes involved in nerve growth factor(NGF)-stimulated transcription were significantly activated.The upregulation of genes linked to the ribonucleic acid(RNA)-induced silencing complex(RISC)suggested a potential role for posttranscriptional regulation in the interac-tion between the vaccinia virus and the host.In the later stages of infection,pathways such as extracellular matrix organization,neutrophil degranulation,complement and interferon responses,translation,and pro-grammed cell death are largely inhibited.A significant number of host genes exhibit correlations with changes in the expression levels of viral genes.The host genes that are negatively correlated with viral genes are mainly enriched in pathways associated with translation and the response to viral infection.This study significantly contributes to advancing our understanding of the dynamics between the vaccinia virus and the host,improv-ing the application of VTTs and facilitating the development of effective vaccines against diseases such as smallpox and monkeypox.