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A zebrafish NLRX1 isoform downregulates fish IFN responses by targeting the adaptor STING.
Zhao, Xiang; An, Li-Li; Gong, Xiu-Ying; Dan, Cheng; Qu, Zi-Ling; Sun, Hao-Yu; Guo, Wen-Hao; Gui, Jian-Fang; Zhang, Yi-Bing.
Afiliación
  • Zhao X; Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
  • An L-L; Yue lu shan Lab, Fisheries College, Hunan Agricultural University, Changsha, China.
  • Gong X-Y; Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
  • Dan C; University of Chinese Academy of Sciences, Beijing, China.
  • Qu Z-L; Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
  • Sun H-Y; University of Chinese Academy of Sciences, Beijing, China.
  • Guo W-H; Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
  • Gui J-F; University of Chinese Academy of Sciences, Beijing, China.
  • Zhang Y-B; Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
J Virol ; 98(2): e0180123, 2024 Feb 20.
Article en En | MEDLINE | ID: mdl-38193691
ABSTRACT
In mammals, NLRX1 is a unique member of the nucleotide-binding domain and leucine-rich repeat (NLR) family showing an ability to negatively regulate IFN antiviral immunity. Intron-containing genes, including NLRX1, have more than one transcript due to alternative splicing; however, little is known about the function of its splicing variants. Here, we identified a transcript variant of NLRX1 in zebrafish (Danio rerio), termed NLRX1-tv4, as a negative regulator of fish IFN response. Zebrafish NLRX1-tv4 was slightly induced by viral infection, with an expression pattern similar to the full-length NLRX1. Despite the lack of an N-terminal domain that exists in the full-length NLRX1, overexpression of NLRX1-tv4 still impaired fish IFN antiviral response and promoted viral replication in fish cells, similar to the full-length NLRX1. Mechanistically, NLRX1-tv4 targeted STING for proteasome-dependent protein degradation by recruiting an E3 ubiquitin ligase RNF5 to drive the K48-linked ubiquitination, eventually downregulating the IFN antiviral response. Mapping of NLRX1-tv4 domains showed that its N-terminal and C-terminal regions exhibited a similar potential to inhibit STING-mediated IFN antiviral response. Our findings reveal that like the full-length NLRX1, zebrafish NLRX-tv4 functions as an inhibitor to shape fish IFN antiviral response.IMPORTANCEIn this study, we demonstrate that a transcript variant of zebrafish NLRX1, termed NLRX1-tv4, downregulates fish IFN response and promotes virus replication by targeting STING for protein degradation and impairing the interaction of STING and TBK1 and that its N- and C-terminus exhibit a similar inhibitory potential. Our results are helpful in clarifying the current contradictory understanding of structure and function of vertebrate NLRX1s.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Pez Cebra / Proteínas Mitocondriales / Proteínas de la Membrana Límite: Animals Idioma: En Revista: J Virol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Pez Cebra / Proteínas Mitocondriales / Proteínas de la Membrana Límite: Animals Idioma: En Revista: J Virol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos