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

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Science  24 Nov 2017:
Vol. 358, Issue 6366, pp. 1051-1055
DOI: 10.1126/science.aao0409

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Host RNA helps promote viral replication

Viruses exploit host metabolic networks for survival. Wang et al. identified a long noncoding RNA (lncRNA) that enhances replication of multiple viruses in both mouse and human cells (see the Perspective by Kotzin et al). The expression of this cytoplasmic lncRNA was induced by viruses and independent of type I interferon. The lncRNA directly bound to and stimulated the metabolic enzyme glutamic-oxaloacetic transaminase. This viral strategy may have relevance for clinical diseases involving metabolic dysfunction and viral infection.

Science, this issue p. 1051; see also p. 993


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.

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