Interferon Regulatory Factors IRF1 and IRF7 Directly Regulate Gene Expression in Bats in Response to Viral Infection.

Abstract:

:Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.

journal_name

Cell Rep

journal_title

Cell reports

authors

Irving AT,Zhang Q,Kong PS,Luko K,Rozario P,Wen M,Zhu F,Zhou P,Ng JHJ,Sobota RM,Wang LF

doi

10.1016/j.celrep.2020.108345

subject

Has Abstract

pub_date

2020-11-03 00:00:00

pages

108345

issue

5

issn

2211-1247

pii

S2211-1247(20)31334-6

journal_volume

33

pub_type

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