The ETS transcription factor ELF1 regulates a broadly antiviral program distinct from the type I interferon response

English version

Autoři: Leon Louis Seifert ^aff001; Clara Si ^aff002; Debjani Saha ^aff003; Mohammad Sadic ^aff002; Maren de Vries ^aff002; Sarah Ballentine ^aff002; Aaron Briley ^aff002; Guojun Wang ^aff003; Ana M. Valero-Jimenez ^aff002; Adil Mohamed ^aff002; Uwe Schaefer ^aff005; Hong M. Moulton ^aff006; Adolfo García-Sastre ^aff003; Shashank Tripathi ^aff003; Brad R. Rosenberg ^aff003; Meike Dittmann ^aff002
Působiště autorů: Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America ^aff001; Department of Microbiology, New York University School of Medicine, New York, New York, United States of America ^aff002; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America ^aff003; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America ^aff004; Laboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, New York, United States of America ^aff005; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, Oregon, United States of America ^aff006; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America ^aff007; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America ^aff008; Microbiology and Cell Biology Department, Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India ^aff009
Vyšlo v časopise: The ETS transcription factor ELF1 regulates a broadly antiviral program distinct from the type I interferon response. PLoS Pathog 15(11): e32767. doi:10.1371/journal.ppat.1007634
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1007634

Souhrn

Induction of vast transcriptional programs is a central event of innate host responses to viral infections. Here we report a transcriptional program with potent antiviral activity, driven by E74-like ETS transcription factor 1 (ELF1). Using microscopy to quantify viral infection over time, we found that ELF1 inhibits eight diverse RNA and DNA viruses after multi-cycle replication. Elf1 deficiency results in enhanced susceptibility to influenza A virus infections in mice. ELF1 does not feed-forward to induce interferons, and ELF1’s antiviral effect is not abolished by the absence of STAT1 or by inhibition of JAK phosphorylation. Accordingly, comparative expression analyses by RNA-seq revealed that the ELF1 transcriptional program is distinct from interferon signatures. Thus, ELF1 provides an additional layer of the innate host response, independent from the action of type I interferons.

Klíčová slova:

DNA transcription – Gene expression – Influenza A virus – Influenza viruses – Interferons – Transcription factors – Viral replication – Antiviral immune response

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