tetano
Editor, Senior Moderator
Sci Signal
. 2024 Apr 9;17(831):eadg7867.
doi: 10.1126/scisignal.adg7867. Epub 2024 Apr 9. Miz1 represses type I interferon production and limits viral clearance during influenza A virus infection
Wenjiao Wu[SUP] 1 2 3 [/SUP], Vinothini Arunagiri[SUP] 1 [/SUP], Hanh Chi Do-Umehara[SUP] 1 [/SUP], Cong Chen[SUP] 4 [/SUP], Shuyin Gu[SUP] 2 [/SUP], Indrani Biswas[SUP] 1 [/SUP], Karen M Ridge[SUP] 4 [/SUP], G R Scott Budinger[SUP] 4 [/SUP], Shuwen Liu[SUP] 2 5 [/SUP], Jing Liu[SUP] 1 [/SUP]
Affiliations
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.
. 2024 Apr 9;17(831):eadg7867.
doi: 10.1126/scisignal.adg7867. Epub 2024 Apr 9. Miz1 represses type I interferon production and limits viral clearance during influenza A virus infection
Wenjiao Wu[SUP] 1 2 3 [/SUP], Vinothini Arunagiri[SUP] 1 [/SUP], Hanh Chi Do-Umehara[SUP] 1 [/SUP], Cong Chen[SUP] 4 [/SUP], Shuyin Gu[SUP] 2 [/SUP], Indrani Biswas[SUP] 1 [/SUP], Karen M Ridge[SUP] 4 [/SUP], G R Scott Budinger[SUP] 4 [/SUP], Shuwen Liu[SUP] 2 5 [/SUP], Jing Liu[SUP] 1 [/SUP]
Affiliations
- PMID: 38593156
- DOI: 10.1126/scisignal.adg7867
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.