RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity
Virus-derived double-stranded RNA (dsRNA) molecules containing a triphosphate group at the 5′ end are natural ligands of retinoic acid-inducible gene I (RIG-I). The cellular pathways and proteins induced by RIG-I are an essential part of the innate immune response against viral infections. Starting...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2019
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| Online Access: | https://hdl.handle.net/10356/106854 http://hdl.handle.net/10220/49675 |
| _version_ | 1826128745972367360 |
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| author | Fink, Katja Ho, Victor Yong, Hui Yee Chevrier, Marion Narang, Vipin Lum, Josephine Toh, Ying-Xiu Lee, Bernett Chen, Jinmiao Tan, Ern Yu Luo, Dahai |
| author2 | Williams, Bryan RG. |
| author_facet | Williams, Bryan RG. Fink, Katja Ho, Victor Yong, Hui Yee Chevrier, Marion Narang, Vipin Lum, Josephine Toh, Ying-Xiu Lee, Bernett Chen, Jinmiao Tan, Ern Yu Luo, Dahai |
| author_sort | Fink, Katja |
| collection | NTU |
| description | Virus-derived double-stranded RNA (dsRNA) molecules containing a triphosphate group at the 5′ end are natural ligands of retinoic acid-inducible gene I (RIG-I). The cellular pathways and proteins induced by RIG-I are an essential part of the innate immune response against viral infections. Starting from a previously published RNA scaffold (3p10L), we characterized an optimized small dsRNA hairpin (called 3p10LG9, 25 nucleotides [nt] in length) as a highly efficient RIG-I activator. Dengue virus (DENV) infection in cell lines and primary human skin cells could be prevented and restricted through 3p10LG9-mediated activation of RIG‐I. This antiviral effect was RIG-I and interferon signal dependent. The effect was temporary and was reversed above a saturating concentration of RIG-I ligand. This finding revealed an effective feedback loop that controls potentially damaging inflammatory effects of the RIG-I response, at least in immune cells. Our results show that the small RIG-I activator 3p10LG9 can confer short-term protection against DENV and can be further explored as an antiviral treatment in humans. |
| first_indexed | 2024-10-01T07:29:56Z |
| format | Journal Article |
| id | ntu-10356/106854 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:29:56Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1068542020-11-01T05:28:10Z RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity Fink, Katja Ho, Victor Yong, Hui Yee Chevrier, Marion Narang, Vipin Lum, Josephine Toh, Ying-Xiu Lee, Bernett Chen, Jinmiao Tan, Ern Yu Luo, Dahai Williams, Bryan RG. School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Dengue RIG-I Science::Biological sciences Virus-derived double-stranded RNA (dsRNA) molecules containing a triphosphate group at the 5′ end are natural ligands of retinoic acid-inducible gene I (RIG-I). The cellular pathways and proteins induced by RIG-I are an essential part of the innate immune response against viral infections. Starting from a previously published RNA scaffold (3p10L), we characterized an optimized small dsRNA hairpin (called 3p10LG9, 25 nucleotides [nt] in length) as a highly efficient RIG-I activator. Dengue virus (DENV) infection in cell lines and primary human skin cells could be prevented and restricted through 3p10LG9-mediated activation of RIG‐I. This antiviral effect was RIG-I and interferon signal dependent. The effect was temporary and was reversed above a saturating concentration of RIG-I ligand. This finding revealed an effective feedback loop that controls potentially damaging inflammatory effects of the RIG-I response, at least in immune cells. Our results show that the small RIG-I activator 3p10LG9 can confer short-term protection against DENV and can be further explored as an antiviral treatment in humans. ASTAR (Agency for Sci., Tech. and Research, S’pore) NMRC (Natl Medical Research Council, S’pore) Published version 2019-08-16T07:56:35Z 2019-12-06T22:19:47Z 2019-08-16T07:56:35Z 2019-12-06T22:19:47Z 2019 Journal Article Ho, V., Yong, H. Y., Chevrier, M., Narang, V., Lum, J., Toh, Y.-X., . . . Fink, K. (2019). RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity. Journal of Virology, 93(14). doi:10.1128/JVI.00102-19 0022-538X https://hdl.handle.net/10356/106854 http://hdl.handle.net/10220/49675 10.1128/JVI.00102-19 en Journal of Virology © 2019 Ho et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International license. 18 p. application/pdf |
| spellingShingle | Dengue RIG-I Science::Biological sciences Fink, Katja Ho, Victor Yong, Hui Yee Chevrier, Marion Narang, Vipin Lum, Josephine Toh, Ying-Xiu Lee, Bernett Chen, Jinmiao Tan, Ern Yu Luo, Dahai RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity |
| title | RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity |
| title_full | RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity |
| title_fullStr | RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity |
| title_full_unstemmed | RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity |
| title_short | RIG-I activation by a designer short RNA ligand protects human immune cells against dengue virus infection without causing cytotoxicity |
| title_sort | rig i activation by a designer short rna ligand protects human immune cells against dengue virus infection without causing cytotoxicity |
| topic | Dengue RIG-I Science::Biological sciences |
| url | https://hdl.handle.net/10356/106854 http://hdl.handle.net/10220/49675 |
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