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

• Published in: Journal of medical virology Vol. 95; no. 8; pp. e29041 - n/a
• Main Authors: Liu, Wei, Lu, Jia‐Yin, Wang, Ya‐Jun, Xu, Xin‐Xin, Chen, Yu‐Chen, Yu, Sai‐Xi, Xiang, Xiao‐Wei, Chen, Xue‐Zhu, Jiu, Yaming, Gao, Hai, Sheng, Mengyao, Chen, Zheng‐Jun, Hu, Xinyao, Li, Dong, Maiuri, Paolo, Huang, Xinxin, Ying, Tianlei, Xu, Guo‐Liang, Pang, Dai‐Wen, Zhang, Zhi‐Ling, Liu, Baohong, Liu, Yan‐Jun
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2023
• Subjects: Actin; Cell migration; Cell Movement; cellular effect; Cytoskeleton; Depolymerization; Disease Outbreaks; Epithelial Cells; Epithelium; Fibers; Genetic transformation; Humans; Mpox; Mpox (monkeypox); Pathogenesis; Phenotypes; Public health; research and analysis methods; RhoA protein; transformation; Transformations; Vaccinia virus; Virology; virus imaging techniques; Viruses; cellular effect; virus imaging techniques; vaccinia virus; transformation; research and analysis methods
• ISSN: 0146-6615; 1096-9071; 1096-9071
• DOI: 10.1002/jmv.29041

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, the mechanism underlying this type of cell migration remains 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 epithelial–mesenchymal transition‐like transformation, during which they lose intercellular junctions and acquire the migratory capacity to promote viral spreading. After transformation, VACV‐hijacked RhoA signaling significantly alters cellular morphology and rearranges the actin cytoskeleton involving the depolymerization of robust actin stress fibers, leading‐edge protrusion formation, and the rear‐edge recontraction, which coordinates VACV‐induced cell migration. 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.