TRIM30α Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING


Negative-feedback regulation is a broad and pivotal biological event to maintain the homeostasis of the host. Viral DNA species derived from DNA viruses or retroviruses can activate STING signaling to produce pro-inflammatory cytokines and type I interferon, which further recruit immune cells or induce interferon stimulated genes (ISGs) to clear viral infection respectively. However, excessive STING-signaling activation has been shown to induce autoimmune disorders. Thus, it is important to finely turn off STING signaling. Here we demonstrate that TRIM30α is rapidly induced followed by STING activation. Trim30α-deficient mice show more resistance to infection by DNA viruses. Meanwhile, knockdown or genetic ablation of TRIM30α augments the type I IFNs and IL-6 responses to intracellular DNA and DNA viruses. Biochemical analyses show that TRIM30α interacts with STING and promotes the degradation of STING via K48-linked ubiquitination at Lys275. These findings demonstrate that induced TRIM30α is a negative-feedback regulator of STING pathway activation triggered by DNA and DNA viruses, which helps the host to avoid excessive response and maintain homeostasis.


Vyšlo v časopise: TRIM30α Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1005012
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1005012

Souhrn

Negative-feedback regulation is a broad and pivotal biological event to maintain the homeostasis of the host. Viral DNA species derived from DNA viruses or retroviruses can activate STING signaling to produce pro-inflammatory cytokines and type I interferon, which further recruit immune cells or induce interferon stimulated genes (ISGs) to clear viral infection respectively. However, excessive STING-signaling activation has been shown to induce autoimmune disorders. Thus, it is important to finely turn off STING signaling. Here we demonstrate that TRIM30α is rapidly induced followed by STING activation. Trim30α-deficient mice show more resistance to infection by DNA viruses. Meanwhile, knockdown or genetic ablation of TRIM30α augments the type I IFNs and IL-6 responses to intracellular DNA and DNA viruses. Biochemical analyses show that TRIM30α interacts with STING and promotes the degradation of STING via K48-linked ubiquitination at Lys275. These findings demonstrate that induced TRIM30α is a negative-feedback regulator of STING pathway activation triggered by DNA and DNA viruses, which helps the host to avoid excessive response and maintain homeostasis.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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