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Article

Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection

by
Jingyu Wang
1,
Yawei Teng
1,
Guanshu Zhao
1,
Fang Li
1,
Ali Hou
1,2,
Bo Sun
1,2,
Wei Kong
1,2,
Feng Gao
1,2,
Linjun Cai
1,2,* and
Chunlai Jiang
1,2,*
1
National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, China
2
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Science, Jilin University, Changchun 130012, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1537; https://doi.org/10.3390/ijms20071537
Submission received: 14 February 2019 / Revised: 22 March 2019 / Accepted: 25 March 2019 / Published: 27 March 2019
(This article belongs to the Section Molecular Microbiology)
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Abstract

The human diploid cell line Medical Research Council -5 (MRC-5) is commonly utilized for vaccine development. Although a rabies vaccine developed in cultured MRC-5 cells exists, the poor susceptibility of MRC-5 cells to the rabies virus (RABV) infection limits the potential yield of this vaccine. The underlying mechanism of MRC-5 cell resistance to RABV infection remains unknown. In this study, we demonstrate that viral infection increased exosomal release from MRC-5 cells; conversely, blocking exosome release promoted RABV infection in MRC-5 cells. Additionally, RABV infection up-regulated microRNA (miR)-423-5p expression in exosomes, resulting in feedback inhibition of RABV replication by abrogating the inhibitory effect of suppressor of cytokine signaling 3 (SOCS3) on type I interferon (IFN) signaling. Furthermore, intercellular delivery of miR-423-5p by exosomes inhibited RABV replication in MRC-5 cells. We also show that RABV infection increased IFN-β production in MRC-5 cells and that blocking the type I IFN receptor promoted RABV infection. In conclusion, MRC-5 cells were protected from RABV infection by the intercellular delivery of exosomal miR-423-5p and the up-regulation of IFN-β. These findings reveal novel antiviral mechanisms in MRC-5 cells against RABV infection. miR-423-5p, exosomes, and IFN signaling pathways may therefore be potential targets for improving MRC-5 cell-based rabies vaccine production.
Keywords: host cell defense; microRNA; SOCS3; vaccine; rabies virus; miR-423-5p host cell defense; microRNA; SOCS3; vaccine; rabies virus; miR-423-5p
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MDPI and ACS Style

Wang, J.; Teng, Y.; Zhao, G.; Li, F.; Hou, A.; Sun, B.; Kong, W.; Gao, F.; Cai, L.; Jiang, C. Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection. Int. J. Mol. Sci. 2019, 20, 1537. https://doi.org/10.3390/ijms20071537

AMA Style

Wang J, Teng Y, Zhao G, Li F, Hou A, Sun B, Kong W, Gao F, Cai L, Jiang C. Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection. International Journal of Molecular Sciences. 2019; 20(7):1537. https://doi.org/10.3390/ijms20071537

Chicago/Turabian Style

Wang, Jingyu, Yawei Teng, Guanshu Zhao, Fang Li, Ali Hou, Bo Sun, Wei Kong, Feng Gao, Linjun Cai, and Chunlai Jiang. 2019. "Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection" International Journal of Molecular Sciences 20, no. 7: 1537. https://doi.org/10.3390/ijms20071537

APA Style

Wang, J., Teng, Y., Zhao, G., Li, F., Hou, A., Sun, B., Kong, W., Gao, F., Cai, L., & Jiang, C. (2019). Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection. International Journal of Molecular Sciences, 20(7), 1537. https://doi.org/10.3390/ijms20071537

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