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TRIM29 Negatively Regulates the Type I IFN Production in Response to RNA Virus.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Jul 01; Vol. 201 (1), pp. 183-192. Date of Electronic Publication: 2018 May 16. - Publication Year :
- 2018
-
Abstract
- The innate immunity is critically important in protection against virus infections, and in the case of RNA viral infections, the signaling mechanisms that initiate robust protective innate immunity without triggering autoimmune inflammation remain incompletely defined. In this study, we found the E3 ligase TRIM29 was specifically expressed in poly I:C-stimulated human myeloid dendritic cells. The induced TRIM29 played a negative role in type I IFN production in response to poly I:C or dsRNA virus reovirus infection. Importantly, the challenge of wild-type mice with reovirus led to lethal infection. In contrast, deletion of TRIM29 protected the mice from this developing lethality. Additionally, TRIM29 <superscript>-/-</superscript> mice have lower titers of reovirus in the heart, intestine, spleen, liver, and brain because of elevated production of type I IFN. Mechanistically, TRIM29 was shown to interact with MAVS and subsequently induce its K11-linked ubiquitination and degradation. Taken together, TRIM29 regulates negatively the host innate immune response to RNA virus, which could be employed by RNA viruses for viral pathogenesis.<br /> (Copyright © 2018 by The American Association of Immunologists, Inc.)
- Subjects :
- Adaptor Proteins, Signal Transducing metabolism
Animals
Cells, Cultured
Dendritic Cells immunology
Humans
Interferon Type I immunology
Mice
Mice, Knockout
Poly I-C
Transcription Factors genetics
Ubiquitination
Immunity, Innate immunology
Interferon Type I biosynthesis
Reoviridae immunology
Reoviridae Infections immunology
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 201
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 29769269
- Full Text :
- https://doi.org/10.4049/jimmunol.1701569