Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection
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. Th...
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MDPI AG
2019-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/20/7/1537 |
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| author | Jingyu Wang Yawei Teng Guanshu Zhao Fang Li Ali Hou Bo Sun Wei Kong Feng Gao Linjun Cai Chunlai Jiang |
| author_facet | Jingyu Wang Yawei Teng Guanshu Zhao Fang Li Ali Hou Bo Sun Wei Kong Feng Gao Linjun Cai Chunlai Jiang |
| author_sort | Jingyu Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:16:40Z |
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| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T15:16:40Z |
| publishDate | 2019-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-58082d4aa5b24d7ca3f9281172a984732022-12-22T02:41:50ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-03-01207153710.3390/ijms20071537ijms20071537Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus InfectionJingyu Wang0Yawei Teng1Guanshu Zhao2Fang Li3Ali Hou4Bo Sun5Wei Kong6Feng Gao7Linjun Cai8Chunlai Jiang9National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaNational Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, ChinaThe 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.https://www.mdpi.com/1422-0067/20/7/1537host cell defensemicroRNASOCS3vaccinerabies virusmiR-423-5p |
| spellingShingle | Jingyu Wang Yawei Teng Guanshu Zhao Fang Li Ali Hou Bo Sun Wei Kong Feng Gao Linjun Cai Chunlai Jiang Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection International Journal of Molecular Sciences host cell defense microRNA SOCS3 vaccine rabies virus miR-423-5p |
| title | Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection |
| title_full | Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection |
| title_fullStr | Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection |
| title_full_unstemmed | Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection |
| title_short | Exosome-Mediated Delivery of Inducible miR-423-5p Enhances Resistance of MRC-5 Cells to Rabies Virus Infection |
| title_sort | exosome mediated delivery of inducible mir 423 5p enhances resistance of mrc 5 cells to rabies virus infection |
| topic | host cell defense microRNA SOCS3 vaccine rabies virus miR-423-5p |
| url | https://www.mdpi.com/1422-0067/20/7/1537 |
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