Characterizing the role of Tupaia DNA damage inducible transcript 3 (DDIT3) gene in viral infections
Zheng, X; Xu, L; Ye, MS; Gu, TL; Yao, YL; Lv, LB; Yu, DD; Yao, YG
2022
发表期刊DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
ISSN0145-305X
卷号127
摘要DNA damage inducible transcript 3 (DDIT3, also known as CHOP) belongs to the CCAAT/enhancer-binding protein (C/EBP) family and plays an essential role in endoplasmic reticulum stress. Here, we characterized the potential role of the Chinese tree shrew (Tupaia belangeri chinensis) DDIT3 (tDDIT3) in viral infections. The tDDIT3 protein is highly conserved and has a species-specific insertion of the SQSS repeat upstream of the Cterminal basic-leucine zipper (bZIP) domain. Phylogenetic analysis of DDIT3 protein sequences of tree shrew and related mammals indicated a closer genetic affinity between tree shrew and primates than between tree shrew and rodents. Three positively selected sites (PSSs: Glu83, Pro93, and Ser172) were identified in tDDIT3 based on the branch-site model. Expression analysis of tDDIT3 showed a constitutively expressed level in different tissues and a significantly increased level in tree shrew cells upon herpes simplex virus type 1 (HSV-1) and Newcastle disease virus (NDV) infections. Overexpression of tDDIT3 significantly increased the production of HSV-1 and vesicular stomatitis virus (VSV) in tree shrew primary renal cells (TSPRCs), whereas tDDIT3 knockout in tree shrew stable cell line (TSR6 cells) had an inhibitory effect on virus production. The enhanced effect on viral infection by tDDIT3 was not associated with the three PSSs. Mechanistically, tDDIT3 overexpression inhibited type I IFN signaling. tDDIT3 interacted with tMAVS through CARD and PRR domains, but not with other immune-related factors such as tMDA5, tSTING and tTBK1. Collectively, our results revealed tDDIT3 as a negative regulator for virus infection.
收录类别sci
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/13483
专题科研部门_疾病机理遗传学和进化医学学科组(姚永刚)
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Zheng, X,Xu, L,Ye, MS,et al. Characterizing the role of Tupaia DNA damage inducible transcript 3 (DDIT3) gene in viral infections[J]. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY,2022,127.
APA Zheng, X.,Xu, L.,Ye, MS.,Gu, TL.,Yao, YL.,...&Yao, YG.(2022).Characterizing the role of Tupaia DNA damage inducible transcript 3 (DDIT3) gene in viral infections.DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY,127.
MLA Zheng, X,et al."Characterizing the role of Tupaia DNA damage inducible transcript 3 (DDIT3) gene in viral infections".DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 127(2022).
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