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An IRF-3-, IRF-5-, and IRF-7-Independent Pathway of Dengue Viral Resistance Utilizes IRF-1 to Stimulate Type I and II Interferon Responses.


ABSTRACT: Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that translate viral recognition into antiviral responses, including type I interferon (IFN) production. Dengue virus (DENV) and other clinically important flaviviruses are suppressed by type I IFN. While mice lacking the type I IFN receptor (Ifnar1-/-) succumb to DENV infection, we found that mice deficient in three transcription factors controlling type I IFN production (Irf3-/-Irf5-/-Irf7-/- triple knockout [TKO]) survive DENV challenge. DENV infection of TKO mice resulted in minimal type I IFN production but a robust type II IFN (IFN-?) response. Using loss-of-function approaches for various molecules, we demonstrate that the IRF-3-, IRF-5-, IRF-7-independent pathway predominantly utilizes IFN-? and, to a lesser degree, type I IFNs. This pathway signals via IRF-1 to stimulate interleukin-12 (IL-12) production and IFN-? response. These results reveal a key antiviral role for IRF-1 by activating both type I and II IFN responses during DENV infection.

SUBMITTER: Carlin AF 

PROVIDER: S-EPMC5696617 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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An IRF-3-, IRF-5-, and IRF-7-Independent Pathway of Dengue Viral Resistance Utilizes IRF-1 to Stimulate Type I and II Interferon Responses.

Carlin Aaron F AF   Plummer Emily M EM   Vizcarra Edward A EA   Sheets Nicholas N   Joo Yunichel Y   Tang William W   Day Jeremy J   Greenbaum Jay J   Glass Christopher K CK   Diamond Michael S MS   Shresta Sujan S  

Cell reports 20171101 6


Interferon-regulatory factors (IRFs) are a family of transcription factors (TFs) that translate viral recognition into antiviral responses, including type I interferon (IFN) production. Dengue virus (DENV) and other clinically important flaviviruses are suppressed by type I IFN. While mice lacking the type I IFN receptor (Ifnar1<sup>-/-</sup>) succumb to DENV infection, we found that mice deficient in three transcription factors controlling type I IFN production (Irf3<sup>-/-</sup>Irf5<sup>-/-</  ...[more]

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