RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death
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 effectiv...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-06-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/6/1476 |
| _version_ | 1797565080976490496 |
|---|---|
| author | Mirjam Schilling Anne Bridgeman Nicki Gray Jonny Hertzog Philip Hublitz Alain Kohl Jan Rehwinkel |
| author_facet | Mirjam Schilling Anne Bridgeman Nicki Gray Jonny Hertzog Philip Hublitz Alain Kohl Jan Rehwinkel |
| author_sort | Mirjam Schilling |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:06:54Z |
| format | Article |
| id | doaj.art-3748a93844d043d385082590838025b5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:06:54Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3748a93844d043d385082590838025b52023-11-20T04:02:41ZengMDPI AGCells2073-44092020-06-0196147610.3390/cells9061476RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell DeathMirjam Schilling0Anne Bridgeman1Nicki Gray2Jonny Hertzog3Philip Hublitz4Alain Kohl5Jan Rehwinkel6Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UKMedical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UKMRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UKMedical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UKGenome Engineering Facility, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UKMRC-Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, UKMedical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UKThe 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.https://www.mdpi.com/2073-4409/9/6/1476Zika virusIFNRIG-IMDA5apoptosisNS5 |
| spellingShingle | Mirjam Schilling Anne Bridgeman Nicki Gray Jonny Hertzog Philip Hublitz Alain Kohl Jan Rehwinkel RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death Cells Zika virus IFN RIG-I MDA5 apoptosis NS5 |
| title | RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death |
| title_full | RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death |
| title_fullStr | RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death |
| title_full_unstemmed | RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death |
| title_short | RIG-I Plays a Dominant Role in the Induction of Transcriptional Changes in Zika Virus-Infected Cells, which Protect from Virus-Induced Cell Death |
| title_sort | rig i plays a dominant role in the induction of transcriptional changes in zika virus infected cells which protect from virus induced cell death |
| topic | Zika virus IFN RIG-I MDA5 apoptosis NS5 |
| url | https://www.mdpi.com/2073-4409/9/6/1476 |
| work_keys_str_mv | AT mirjamschilling rigiplaysadominantroleintheinductionoftranscriptionalchangesinzikavirusinfectedcellswhichprotectfromvirusinducedcelldeath AT annebridgeman rigiplaysadominantroleintheinductionoftranscriptionalchangesinzikavirusinfectedcellswhichprotectfromvirusinducedcelldeath AT nickigray rigiplaysadominantroleintheinductionoftranscriptionalchangesinzikavirusinfectedcellswhichprotectfromvirusinducedcelldeath AT jonnyhertzog rigiplaysadominantroleintheinductionoftranscriptionalchangesinzikavirusinfectedcellswhichprotectfromvirusinducedcelldeath AT philiphublitz rigiplaysadominantroleintheinductionoftranscriptionalchangesinzikavirusinfectedcellswhichprotectfromvirusinducedcelldeath AT alainkohl rigiplaysadominantroleintheinductionoftranscriptionalchangesinzikavirusinfectedcellswhichprotectfromvirusinducedcelldeath AT janrehwinkel rigiplaysadominantroleintheinductionoftranscriptionalchangesinzikavirusinfectedcellswhichprotectfromvirusinducedcelldeath |