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Science. 2017 Nov 24;358(6366):1051-1055. doi: 10.1126/science.aao0409. Epub 2017 Oct 26.

An interferon-independent lncRNA promotes viral replication by modulating cellular metabolism.

Wang P1, Xu J2, Wang Y2, Cao X3,2,4.

Author information

1
National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
2
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
3
National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China. caoxt@immunol.org.
4
Department of Immunology and Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.

Abstract

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.

PMID:
29074580
DOI:
10.1126/science.aao0409
[Indexed for MEDLINE]

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