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...

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Autores principales: Vikas Sood, Kiran Bala Sharma, Vishal Gupta, Dhurjhoti Saha, Parashar Dhapola, Manish Sharma, Utsav Sen, Shigetaka Kitajima, Shantanu Chowdhury, Manjula Kalia, Sudhanshu Vrati
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/8ce5b5bafe084c7b89b6e768a4e4585a
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spelling oai:doaj.org-article:8ce5b5bafe084c7b89b6e768a4e4585a2021-12-02T16:06:39ZATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons10.1038/s41598-017-08584-92045-2322https://doaj.org/article/8ce5b5bafe084c7b89b6e768a4e4585a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08584-9https://doaj.org/toc/2045-2322Abstract 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.Vikas SoodKiran Bala SharmaVishal GuptaDhurjhoti SahaParashar DhapolaManish SharmaUtsav SenShigetaka KitajimaShantanu ChowdhuryManjula KaliaSudhanshu VratiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
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.
format article
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
title 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_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_sort atf3 negatively regulates cellular antiviral signaling and autophagy in the absence of type i interferons
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/8ce5b5bafe084c7b89b6e768a4e4585a
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