TRIM29 promotes DNA virus infections by inhibiting innate immune response

Nat Commun. 2017 Oct 16;8(1):945. doi: 10.1038/s41467-017-00101-w.

Junji Xing ¹, Ao Zhang ², Hua Zhang ², Jin Wang ¹, Xian Chang Li ³ ⁴, Mu-Sheng Zeng ⁵ ⁶, Zhiqiang Zhang ⁷ ⁸

Affiliations

1 Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX, 77030, USA.
2 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
3 Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX, 77030, USA. xcli@houstonmethodist.org.
4 Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY, 10065, USA. xcli@houstonmethodist.org.
5 State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. zengmsh@sysucc.org.cn.
6 Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. zengmsh@sysucc.org.cn.
7 Immunobiology and Transplant Science Center, Houston Methodist Research Institute, Houston, TX, 77030, USA. zzhang@houstonmethodist.org.
8 Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY, 10065, USA. zzhang@houstonmethodist.org.

PMID: 29038422 DOI: 10.1038/s41467-017-00101-w

Abstract

Many double-stranded DNA viruses, such as Epstein-Barr virus, can establish persistent Infection, but the underlying virus-host interactions remain poorly understood. Here we report that in human airway epithelial cells Epstein-Barr virus induces TRIM29, a member of the TRIM family of proteins, to inhibit innate immune activation. Knockdown of TRIM29 in airway epithelial cells enhances type I interferon production, and in human nasopharyngeal carcinoma cells results in almost complete Epstein-Barr virus clearance. TRIM29 is also highly induced by cytosolic double-stranded DNA in myeloid dendritic cells. TRIM29 ^-/- mice have lower adenovirus titers in the lung, and are resistant to lethal herpes simplex virus-1 Infection due to enhanced production of type I interferon. Mechanistically, TRIM29 induces K48-linked ubiquitination of Stimulator of interferon genes, a key adaptor in double-stranded DNA-sensing pathway, followed by its rapid degradation. These data demonstrate that Epstein-Barr virus and possible Other double-stranded DNA viruses use TRIM29 to suppress local innate immunity, leading to the persistence of DNA virus infections.Proteins of the TRIM family have regulatory functions in immune signaling, often via ubiquitination of target proteins. Here, the authors show that TRIM29 is induced upon Infection with DNA viruses, resulting in degradation of STING, decreased interferon signaling and increased pathogenicity in mice.

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