TitleThe ETS transcription factor ELF1 regulates a broadly antiviral program distinct from the type I interferon response.
Publication TypeJournal Article
Year of Publication2019
AuthorsSeifert, LLouis, Si, C, Saha, D, Sadic, M, de Vries, M, Ballentine, S, Briley, A, Wang, G, Valero-Jimenez, AM, Mohamed, A, Schaefer, U, Moulton, H, García-Sastre, A, Tripathi, S, Rosenberg, BR, Dittmann, M
JournalPLoS Pathog
Volume15
Issue11
Paginatione1007634
Date Published2019 11
ISSN1553-7374
KeywordsA549 Cells, Animals, Antiviral Agents, Female, Gene Expression Regulation, Humans, Immunity, Innate, Influenza A virus, Interferon Type I, Mice, Mice, Inbred C57BL, NF-kappa B, Nuclear Proteins, Orthomyxoviridae Infections, Phosphorylation, Signal Transduction, STAT1 Transcription Factor, Transcription Factors, Virus Replication
Abstract

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.

DOI10.1371/journal.ppat.1007634
Alternate JournalPLoS Pathog
PubMed ID31682641
PubMed Central IDPMC6932815
Grant ListHHSN272201400008C / AI / NIAID NIH HHS / United States
R01 AI091707 / AI / NIAID NIH HHS / United States
R00 AI121473 / AI / NIAID NIH HHS / United States
K99 AI121473 / AI / NIAID NIH HHS / United States
T32 AI007180 / AI / NIAID NIH HHS / United States
U19 AI135972 / AI / NIAID NIH HHS / United States
R01 AI143639 / AI / NIAID NIH HHS / United States
S10 OD018522 / OD / NIH HHS / United States
DP5 OD012142 / OD / NIH HHS / United States