Report

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

See allHide authors and affiliations

Science  26 Oct 2017:
eaao0409
DOI: 10.1126/science.aao0409

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Abstract

Viruses regulate host metabolic networks to improve their survival. Hardly known are molecules responsive to viral infection that regulate such metabolic changes, which is essential for understanding viral infection. Here we identify a lncRNA induced by multiple viruses, but not by type I interferon (IFN-I), that facilitates viral replication in mouse and human cells. In vivo deficiency of lncRNA-ACOD1 significantly attenuates viral infection through IFN-I/IRF3-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 way of virus-induced lncRNA-mediated metabolic promotion of viral infection, and a potential target for developing broad-acting antiviral therapeutics.

View Full Text