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Sci Rep. 2017 Aug 18;7(1):8789. doi: 10.1038/s41598-017-08584-9.

ATF3 negatively regulates cellular antiviral signaling and autophagy in the absence of type I interferons.

Author information

1
Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Faridabad, 121001, India. vikas@thsti.res.in.
2
Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Faridabad, 121001, India.
3
CSIR-Institute of Genomics and Integrative Biology, Delhi, 110007, India.
4
Faculty of Biological Sciences, Academy of Scientific and Innovative Research (AcSIR), New Delhi, 110025, India.
5
Tokyo Medical and Dental University, Tokyo, 113-0034, Japan.
6
Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Faridabad, 121001, India. vrati@thsti.res.in.
7
Regional Centre for Biotechnology, Faridabad, 121001, India. vrati@thsti.res.in.

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.

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