Miz1 represses type I interferon production and limits viral clearance during influenza A virus infection.

Autor: Wu W; Department of Surgery, College of Medicine, Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA.; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.; Department of Pharmacy, Guangdong Second Provincial General Hospital, 466 Middle Xingang Road, Guangzhou 510317, Guangdong, China., Arunagiri V; Department of Surgery, College of Medicine, Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA., Do-Umehara HC; Department of Surgery, College of Medicine, Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA., Chen C; Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Gu S; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China., Biswas I; Department of Surgery, College of Medicine, Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA., Ridge KM; Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Budinger GRS; Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Liu S; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.; State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China., Liu J; Department of Surgery, College of Medicine, Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA.
Jazyk: angličtina
Zdroj: Science signaling [Sci Signal] 2024 Apr 09; Vol. 17 (831), pp. eadg7867. Date of Electronic Publication: 2024 Apr 09.
DOI: 10.1126/scisignal.adg7867
Abstrakt: Type I interferons (IFNs) are critical for the antiviral immune response, and fine-tuning type I IFN production is critical to effectively clearing viruses without causing harmful immunopathology. We showed that the transcription factor Miz1 epigenetically repressed the expression of genes encoding type I IFNs in mouse lung epithelial cells by recruiting histone deacetylase 1 (HDAC1) to the promoters of Ifna and Ifnb . Loss of function of Miz1 resulted in augmented production of these type I IFNs during influenza A virus (IAV) infection, leading to improved viral clearance in vitro and in vivo. IAV infection induced Miz1 accumulation by promoting the cullin-4B (CUL4B)-mediated ubiquitylation and degradation of the E3 ubiquitin ligase Mule (Mcl-1 ubiquitin ligase E3; also known as Huwe1 or Arf-BP1), which targets Miz1 for degradation. As a result, Miz1 accumulation limited type I IFN production and favored viral replication. This study reveals a previously unrecognized function of Miz1 in regulating antiviral defense and a potential mechanism for influenza viruses to evade host immune defense.
Databáze: MEDLINE