Open AccessTRIM30α Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING
Author(s) -
Yanming Wang,
Qiaoshi Lian,
Bo Yang,
Shanshan Yan,
Haiyan Zhou,
Long He,
Guomei Lin,
ZheXiong Lian,
Zhengfan Jiang,
Bing Sun
Publication year - 2015
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1005012
Subject(s) - biology , sting , ubiquitin ligase , regulator , immune system , dna virus , herpes simplex virus , dna , interferon , microbiology and biotechnology , dna ligase , innate immune system , dna vaccination , virus , virology , ubiquitin , gene , immunology , genetics , genome , engineering , aerospace engineering , immunization
Uncontrolled immune responses to intracellular DNA have been shown to induce autoimmune diseases. Homeostasis regulation of immune responses to cytosolic DNA is critical for limiting the risk of autoimmunity and survival of the host. Here, we report that the E3 ubiquitin ligase tripartite motif protein 30α (TRIM30α) was induced by herpes simplex virus type 1 (HSV-1) infection in dendritic cells (DCs). Knockdown or genetic ablation of TRIM30α augmented the type I IFNs and interleukin-6 response to intracellular DNA and DNA viruses. Trim30α -deficient mice were more resistant to infection by DNA viruses. Biochemical analyses showed that TRIM30α interacted with the stimulator of interferon genes (STING), which is a critical regulator of the DNA-sensing response. Overexpression of TRIM30α promoted the degradation of STING via K48-linked ubiquitination at Lys275 through a proteasome-dependent pathway. These findings indicate that E3 ligase TRIM30α is an important negative-feedback regulator of innate immune responses to DNA viruses by targeting STING.