ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons
Abstract Stringent regulation of antiviral signaling and cellular autophagy is critical for the host response to virus infection. However, little is known how these cellular processes are regulated in the absence of type I interferon signaling. Here, we show that ATF3 is induced following Japanese e...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-08584-9 |
| _version_ | 1818751902328815616 |
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| author | Vikas Sood Kiran Bala Sharma Vishal Gupta Dhurjhoti Saha Parashar Dhapola Manish Sharma Utsav Sen Shigetaka Kitajima Shantanu Chowdhury Manjula Kalia Sudhanshu Vrati |
| author_facet | Vikas Sood Kiran Bala Sharma Vishal Gupta Dhurjhoti Saha Parashar Dhapola Manish Sharma Utsav Sen Shigetaka Kitajima Shantanu Chowdhury Manjula Kalia Sudhanshu Vrati |
| author_sort | Vikas Sood |
| collection | DOAJ |
| description | Abstract Stringent regulation of antiviral signaling and cellular autophagy is critical for the host response to virus infection. However, little is known how these cellular processes are regulated in the absence of type I interferon signaling. Here, we show that ATF3 is induced following Japanese encephalitis virus (JEV) infection, and regulates cellular antiviral and autophagy pathways in the absence of type I interferons in mouse neuronal cells. We have identified new targets of ATF3 and show that it binds to the promoter regions of Stat1, Irf9, Isg15 and Atg5 thereby inhibiting cellular antiviral signaling and autophagy. Consistent with these observations, ATF3-depleted cells showed enhanced antiviral responses and induction of robust autophagy. Furthermore, we show that JEV replication was significantly reduced in ATF3-depleted cells. Our findings identify ATF3 as a negative regulator of antiviral signaling and cellular autophagy in mammalian cells, and demonstrate its important role in JEV life cycle. |
| first_indexed | 2024-12-18T04:42:57Z |
| format | Article |
| id | doaj.art-8ce5b5bafe084c7b89b6e768a4e4585a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:42:57Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8ce5b5bafe084c7b89b6e768a4e4585a2022-12-21T21:20:40ZengNature PortfolioScientific Reports2045-23222017-08-017111710.1038/s41598-017-08584-9ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferonsVikas Sood0Kiran Bala Sharma1Vishal Gupta2Dhurjhoti Saha3Parashar Dhapola4Manish Sharma5Utsav Sen6Shigetaka Kitajima7Shantanu Chowdhury8Manjula Kalia9Sudhanshu Vrati10Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology InstituteVaccine and Infectious Disease Research Centre, Translational Health Science and Technology InstituteVaccine and Infectious Disease Research Centre, Translational Health Science and Technology InstituteCSIR-Institute of Genomics and Integrative BiologyCSIR-Institute of Genomics and Integrative BiologyVaccine and Infectious Disease Research Centre, Translational Health Science and Technology InstituteVaccine and Infectious Disease Research Centre, Translational Health Science and Technology InstituteTokyo Medical and Dental UniversityCSIR-Institute of Genomics and Integrative BiologyVaccine and Infectious Disease Research Centre, Translational Health Science and Technology InstituteVaccine and Infectious Disease Research Centre, Translational Health Science and Technology InstituteAbstract Stringent regulation of antiviral signaling and cellular autophagy is critical for the host response to virus infection. However, little is known how these cellular processes are regulated in the absence of type I interferon signaling. Here, we show that ATF3 is induced following Japanese encephalitis virus (JEV) infection, and regulates cellular antiviral and autophagy pathways in the absence of type I interferons in mouse neuronal cells. We have identified new targets of ATF3 and show that it binds to the promoter regions of Stat1, Irf9, Isg15 and Atg5 thereby inhibiting cellular antiviral signaling and autophagy. Consistent with these observations, ATF3-depleted cells showed enhanced antiviral responses and induction of robust autophagy. Furthermore, we show that JEV replication was significantly reduced in ATF3-depleted cells. Our findings identify ATF3 as a negative regulator of antiviral signaling and cellular autophagy in mammalian cells, and demonstrate its important role in JEV life cycle.https://doi.org/10.1038/s41598-017-08584-9 |
| spellingShingle | Vikas Sood Kiran Bala Sharma Vishal Gupta Dhurjhoti Saha Parashar Dhapola Manish Sharma Utsav Sen Shigetaka Kitajima Shantanu Chowdhury Manjula Kalia Sudhanshu Vrati ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons Scientific Reports |
| title | ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons |
| title_full | ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons |
| title_fullStr | ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons |
| title_full_unstemmed | ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons |
| title_short | ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons |
| title_sort | atf3 negatively regulates cellular antiviral signaling and autophagy in the absence of type i interferons |
| url | https://doi.org/10.1038/s41598-017-08584-9 |
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