Schilling, M., Bridgeman, A., Gray, N., Hertzog, J., Hublitz, P., Kohl, A. and Rehwinkel, J. (2020) RIG-I plays a dominant role in the induction of transcriptional changes in Zika virus-infected cells and protects from virus-induced cell death. Cells, 9(6), 1476. (doi: 10.3390/cells9061476)
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Abstract
The Zika virus (ZIKV) has received much attention due to an alarming increase in cases of neurological disorders including congenital Zika syndrome associated with infection. To date, there is no effective treatment available. An immediate response by the innate immune system is crucial for effective control of the virus. Using CRISPR/Cas9-mediated knockouts in A549 cells, we investigated the individual contributions of the RIG-I-like receptors MDA5 and RIG-I to ZIKV sensing and control of this virus by using a Brazilian ZIKV strain. We show that RIG-I is the main sensor for ZIKV in A549 cells. Surprisingly, we observed that loss of RIG-I and consecutive type I interferon (IFN) production led to virus-induced apoptosis. ZIKV non-structural protein NS5 was reported to interfere with type I IFN receptor signaling. Additionally, we show that ZIKV NS5 inhibits type I IFN induction. Overall, our study highlights the importance of RIG-I-dependent ZIKV sensing for the prevention of virus-induced cell death and shows that NS5 inhibits the production of type I IFN.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was also funded by the Wellcome Trust [Grant Number 100954; J.R.]. J.H. is supported by the European Commission under the Horizon2020 program H2020 MSCA-ITN GA 675278 EDGE. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Kohl, Professor Alain |
| Creator Roles: | |
| Authors: | Schilling, M., Bridgeman, A., Gray, N., Hertzog, J., Hublitz, P., Kohl, A., and Rehwinkel, J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Cells |
| Publisher: | MDPI |
| ISSN: | 2073-4409 |
| ISSN (Online): | 2073-4409 |
| Copyright Holders: | Copyright © 2020 by the authors |
| First Published: | First published in Cells 9(6):1476 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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