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


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): e1007634. doi:10.1371/journal.ppat.1007634
Kategorie: Research Article
doi: 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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