Journal
CELL HOST & MICROBE
Volume 16, Issue 5, Pages 616-626Publisher
CELL PRESS
DOI: 10.1016/j.chom.2014.10.001
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Funding
- National Key Technologies Research and Development Program of China [2013ZX10004-611]
- National Basic Research Program (973) of China [2015CB910502]
- Natural Science Foundation of China [U1305212]
- Intramural grant of the Chinese Academy of Sciences [KJZD-EW-L01-3]
- China Postdoctoral Science Foundation [2012M510585]
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Long noncoding RNAs (lncRNAs) modulate various biological processes, but their role in host antiviral responses is largely unknown. Here we identify a lncRNA as a key regulator of antiviral innate immunity. Following from the observation that a lncRNA that we call negative regulator of antiviral response (NRAV) was dramatically downregulated during infection with several viruses, we ectopically expressed NRAV in human cells or transgenic mice and found that it significantly promotes influenza A virus (IAV) replication and virulence. Conversely, silencing NRAV suppressed IAV replication and virus production, suggesting that reduction of NRAV is part of the host antiviral innate immune response to virus infection. NRAV negatively regulates the initial transcription of multiple critical interferon-stimulated genes (ISGs), including IFITM3 and MxA, by affecting histone modification of these genes. Our results provide evidence for a lncRNA in modulating the antiviral interferon response.
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