气候变化领域集成服务门户(CCPortal): An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism

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DOI	10.1126/science.aao0409
	An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism
	Wang P.; Xu J.; Wang Y.; Cao X.
发表日期	2017
ISSN	0036-8075
起始页码	1051
结束页码	1055
卷号	358 期号:6366
英文摘要	Viruses regulate host metabolic networks to improve their survival. The molecules that are responsive to viral infection and regulate such metabolic changes are hardly known, but are essential for understanding viral infection. Here we identify a long noncoding RNA (lncRNA) that is induced by multiple viruses, but not by type I interferon (IFN-I), and facilitates viral replication in mouse and human cells. In vivo deficiency of lncRNA-ACOD1 (a lncRNA identified by its nearest coding gene Acod1, aconitate decarboxylase 1) significantly attenuates viral infection through IFN-I–IRF3 (interferon regulatory factor 3)–independent pathways. Cytoplasmic lncRNA-ACOD1 directly binds the metabolic enzyme glutamic-oxaloacetic transaminase (GOT2) near the substrate niche, enhancing its catalytic activity. Recombinant GOT2 protein and its metabolites could rescue viral replication upon lncRNA-ACOD1 deficiency and increase lethality. This work reveals a feedback mechanism of virus-induced lncRNA-mediated metabolic promotion of viral infection and a potential target for developing broad-acting antiviral therapeutics. © 2017, American Association for the Advancement of Science. All rights reserved.
英文关键词	aconitate decarboxylase 1; aspartate aminotransferase isoenzyme 2; carboxylyase; interferon; interferon regulatory factor 3; long untranslated RNA; RNA; RNA binding protein; unclassified drug; aconitate decarboxylase; aspartate aminotransferase; carboxylyase; interferon; interferon regulatory factor 3; long untranslated RNA; catalysis; cells and cell components; enzyme; enzyme activity; feedback mechanism; infectious disease; metabolism; metabolite; protein; RNA; viral disease; virus; amino acid sequence; Article; binding site; cell metabolism; dendritic cell; DNA virus; enzyme activity; feedback system; host resistance; human; in vitro study; in vivo study; innate immunity; nonhuman; peritoneum macrophage; priority journal; promoter region; protein binding; RNA interference; RNA sequence; Vaccinia virus; Vesiculovirus; virus infection; virus load; virus replication; animal; genetics; HEK293 cell line; host pathogen interaction; immunology; metabolism; mouse; virology; Animals; Aspartate Aminotransferases; Carboxy-Lyases; HEK293 Cells; Host-Pathogen Interactions; Humans; Interferon Regulatory Factor-3; Interferons; Mice; RNA, Long Noncoding; Virus Diseases; Virus Replication
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/245949
作者单位	National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, Shanghai, 200433, China; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China; Department of Immunology and Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China
推荐引用方式 GB/T 7714	Wang P.,Xu J.,Wang Y.,et al. An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism[J],2017,358(6366).
APA	Wang P.,Xu J.,Wang Y.,&Cao X..(2017).An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism.Science,358(6366).
MLA	Wang P.,et al."An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism".Science 358.6366(2017).