Orf virus impairs tumor-promoting capacity of tumor-derived extracellular vesicles

Oncolytic viruses (OVs) can selectively replicate in tumor cells and trigger anti-tumor immunity. However, it remains unclear whether OVs can target the process of ‘information transmission’ between tumor cells to assist their anti-tumor effects. Uncovering this issue would help to understand the way how OV reshapes tumor microenvironment. Here, we focused on the interaction between oncolytic parapoxvirus (ORFV) and tumor-derived extracellular vesicles (EVs), attempting to reveal the regulatory role of OVs in the process of tumor information transmission. We previously constructed a recombinant orf virus ORFV△ with virulence gene deletion as an anti-tumor agent. We found that tumor-derived EVs could interfere with the anti-tumor growth and metastasis capabilities of ORFV△. Moreover, we also found that ORFV△ inhibited the level of tumor-derived EVs, indicating that ORFV△ and EVs can affect with each other. Notably, ORFV△ can further reprogram microRNA (miRNA) profile in EVs, prompting EVs to enrich a series of miRNAs that target oncogenes in pro-tumor pathways. Subsequently, it was confirmed that the EVs produced by tumors treated with ORFV△ have significantly restricted abilities in promoting tumor cell viability, proliferation, and migration. The above results enrich the anti-tumor mechanism of OV and suggest the necessity of inhibiting tumor-derived EVs during OV-based therapy.