Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration

Liu, W.; Lu, J.-Y.; Wang, Y.-J.; Xu, X.-x.; Chen, Y.-C.; Yu, S.-X.; Xiang, X.-W.; Chen, X.-Z.; Jiu, Y.; Gao, H.; Sheng, M.; Chen, Z.-J.; Hu, X.; Li, D.; Maiuri, P.; Huang, X.; Ying, T.; Xu, G.-L.; Pang, D.-W.; Zhang, Z.-L.; Liu, B.; Liu, Y.-J.

doi:10.1101/2023.02.04.527154

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bioRxiv · 10.1101/2023.02.04.527154

Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration

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Abstract

The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, high-resolution dynamics and mechanisms underlying this type of cell migration remain unclear. Here, we investigate the motility of cells infected by vaccinia virus (VACV), a close relative of monkeypox, through combining multi-omics analyses and high-resolution live-cell imaging. We find that, upon VACV infection, the epithelial cells undergo EMT-like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV-induced mesenchymal migration is highly dependent on the actin cytoskeleton and RhoA signaling, which is responsible for the depolymerization of robust actin stress fibers, the leading-edge protrusion formation, and the rear-edge recontraction. Our study reveals how poxviruses alter the epithelial phenotype and regulate RhoA signaling to induce fast migration, providing a unique perspective to understand the pathogenesis of poxviruses.

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Liu, W., Lu, J.-Y., Wang, Y.-J., Xu, X.-x., Chen, Y.-C., Yu, S.-X., Xiang, X.-W., Chen, X.-Z., Jiu, Y., Gao, H., Sheng, M., Chen, Z.-J., Hu, X., Li, D., Maiuri, P., Huang, X., Ying, T., Xu, G.-L., Pang, D.-W., Zhang, Z.-L., Liu, B., Liu, Y.-J.. 2023-02-05. Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration. https://doi.org/10.1101/2023.02.04.527154

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