article published yes Anna Pereira author Flávia Leite author 36705F98-F248-11E8-B48F-1D18A9856A87 Bruno Brasil author Jamaria Soares Martins author Alice Torres author Paulo Pimenta author Thais Souto Padrón author Paula Tranktman author Paulo Ferreira author Erna Kroon author Cláudio Bonjardim author JoBo department Viral manipulation of transduction pathways associated with key cellular functions such as survival, response to microbial infection, and cytoskeleton reorganization can provide the supportive milieu for a productive infection. Here, we demonstrate that vaccinia virus (VACV) infection leads to activation of the stress-activated protein kinase (SAPK)/extracellular signal-regulated kinase (ERK) 4/7 (MKK4/7)-c-Jun N-terminal protein kinase 1/2 (JNK1/2) pathway; further, the stimulation of this pathway requires postpenetration, prereplicative events in the viral replication cycle. Although the formation of intracellular mature virus (IMV) was not affected in MKK4/7- or JNK1/2-knockout (KO) cells, we did note an accentuated deregulation of microtubule and actin network organization in infected JNK1/2-KO cells. This was followed by deregulated viral trafficking to the periphery and enhanced enveloped particle release. Furthermore, VACV infection induced alterations in the cell contractility and morphology, and cell migration was reduced in the JNK-KO cells. In addition, phosphorylation of proteins implicated with early cell contractility and cell migration, such as microtubule-associated protein 1B and paxillin, respectively, was not detected in the VACV-infected KO cells. In sum, our findings uncover a regulatory role played by the MKK4/7-JNK1/2 pathway in cytoskeleton reorganization during VACV infection. ASM2012 eng 22031940 00029834770001710.1128/JVI.05638-11 861172 - 184 A. Pereira <i>et al.</i>, “A vaccinia virus-driven interplay between the MKK4/7-JNK1/2 pathway and cytoskeleton reorganization,” <i>Journal of Virology</i>, vol. 86, no. 1. ASM, pp. 172–184, 2012. Pereira, Anna, Flávia Leite, Bruno Brasil, Jamaria Soares Martins, Alice Torres, Paulo Pimenta, Thais Souto Padrón, et al. “A Vaccinia Virus-Driven Interplay between the MKK4/7-JNK1/2 Pathway and Cytoskeleton Reorganization.” <i>Journal of Virology</i>. ASM, 2012. <a href="https://doi.org/10.1128/JVI.05638-11">https://doi.org/10.1128/JVI.05638-11</a>. A. Pereira, F. Leite, B. Brasil, J. Soares Martins, A. Torres, P. Pimenta, T. Souto Padrón, P. Tranktman, P. Ferreira, E. Kroon, C. Bonjardim, Journal of Virology 86 (2012) 172–184. Pereira, A., Leite, F., Brasil, B., Soares Martins, J., Torres, A., Pimenta, P., … Bonjardim, C. (2012). A vaccinia virus-driven interplay between the MKK4/7-JNK1/2 pathway and cytoskeleton reorganization. <i>Journal of Virology</i>. ASM. <a href="https://doi.org/10.1128/JVI.05638-11">https://doi.org/10.1128/JVI.05638-11</a> Pereira A, Leite F, Brasil B, Soares Martins J, Torres A, Pimenta P, Souto Padrón T, Tranktman P, Ferreira P, Kroon E, Bonjardim C. 2012. A vaccinia virus-driven interplay between the MKK4/7-JNK1/2 pathway and cytoskeleton reorganization. Journal of Virology. 86(1), 172–184. Pereira A, Leite F, Brasil B, et al. A vaccinia virus-driven interplay between the MKK4/7-JNK1/2 pathway and cytoskeleton reorganization. <i>Journal of Virology</i>. 2012;86(1):172-184. doi:<a href="https://doi.org/10.1128/JVI.05638-11">10.1128/JVI.05638-11</a> Pereira, Anna, et al. “A Vaccinia Virus-Driven Interplay between the MKK4/7-JNK1/2 Pathway and Cytoskeleton Reorganization.” <i>Journal of Virology</i>, vol. 86, no. 1, ASM, 2012, pp. 172–84, doi:<a href="https://doi.org/10.1128/JVI.05638-11">10.1128/JVI.05638-11</a>. 32892018-12-11T12:02:29Z2025-09-30T07:40:18Z