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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartate Aminotransferases / metabolism*
  • Carboxy-Lyases / genetics
  • HEK293 Cells
  • Host-Pathogen Interactions*
  • Humans
  • Interferon Regulatory Factor-3 / metabolism
  • Interferons / immunology
  • Mice
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Virus Diseases / metabolism*
  • Virus Diseases / virology*
  • Virus Replication*


  • Interferon Regulatory Factor-3
  • RNA, Long Noncoding
  • Interferons
  • Aspartate Aminotransferases
  • Carboxy-Lyases
  • aconitate decarboxylase