Annotation of long non-coding RNAs expressed in collaborative cross founder mice in response to respiratory virus infection reveals a new class of interferon-stimulated transcripts

RNA Biol. 2014;11(7):875-90. doi: 10.4161/rna.29442. Epub 2014 Jun 12.


The outcome of respiratory virus infection is determined by a complex interplay of viral and host factors. Some potentially important host factors for the antiviral response, whose functions remain largely unexplored, are long non-coding RNAs (lncRNAs). Here we systematically inferred the regulatory functions of host lncRNAs in response to influenza A virus and severe acute respiratory syndrome coronavirus (SARS-CoV) based on their similarity in expression with genes of known function. We performed total RNA-Seq on viral-infected lungs from eight mouse strains, yielding a large data set of transcriptional responses. Overall 5,329 lncRNAs were differentially expressed after infection. Most of the lncRNAs were co-expressed with coding genes in modules enriched in genes associated with lung homeostasis pathways or immune response processes. Each lncRNA was further individually annotated using a rank-based method, enabling us to associate 5,295 lncRNAs to at least one gene set and to predict their potential cis effects. We validated the lncRNAs predicted to be interferon-stimulated by profiling mouse responses after interferon-α treatment. Altogether, these results provide a broad categorization of potential lncRNA functions and identify subsets of lncRNAs with likely key roles in respiratory virus pathogenesis. These data are fully accessible through the MOuse NOn-Code Lung interactive database (MONOCLdb).

Keywords: collaborative cross; influenza virus; interferon; long non-coding rna; rna-seq; sars-cov.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacology
  • Cell Line
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Influenza A virus / drug effects
  • Influenza A virus / physiology
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / pharmacology
  • Lung / metabolism
  • Lung / virology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Annotation
  • RNA Virus Infections / drug therapy*
  • RNA Virus Infections / genetics*
  • RNA Virus Infections / virology
  • RNA, Long Noncoding / genetics*
  • Sequence Analysis, RNA
  • Severe acute respiratory syndrome-related coronavirus / drug effects
  • Severe acute respiratory syndrome-related coronavirus / physiology


  • Antiviral Agents
  • Interferon-alpha
  • RNA, Long Noncoding