title: 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.
abstract: 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).
authors.affiliation: Department of Microbiology; School of Medicine; University of Washington; Seattle, WA USA; Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Josset
authors.affiliation: Department of Microbiology; School of Medicine; University of Washington; Seattle, WA USA; Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tchitchek
authors.affiliation: Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA; Department of Epidemiology; University of North Carolina-Chapel Hill; Chapel Hill, NC USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Gralinski
authors.affiliation: Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA; Department of Genetics; University of North Carolina-Chapel Hill; Chapel Hill, NC USA.
authors.forename: Martin T
authors.initials: MT
authors.lastname: Ferris
authors.affiliation: Department of Pathobiological Sciences; Influenza Research Institute; University of Wisconsin-Madison; Madison, WI USA.
authors.forename: Amie J
authors.initials: AJ
authors.lastname: Eisfeld
authors.affiliation: Department of Microbiology; School of Medicine; University of Washington; Seattle, WA USA; Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Green
authors.affiliation: Department of Microbiology; School of Medicine; University of Washington; Seattle, WA USA; Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Thomas
authors.affiliation: Department of Microbiology; School of Medicine; University of Washington; Seattle, WA USA; Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tisoncik-Go
authors.affiliation: Illumina, Inc.; San Diego, CA USA.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Schroth
authors.affiliation: Department of Pathobiological Sciences; Influenza Research Institute; University of Wisconsin-Madison; Madison, WI USA.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.affiliation: Department of Genetics; University of North Carolina-Chapel Hill; Chapel Hill, NC USA.
authors.forename: Fernando Pardo
authors.initials: FP
authors.lastname: Manuel de Villena
authors.affiliation: Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA; Department of Epidemiology; University of North Carolina-Chapel Hill; Chapel Hill, NC USA.
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
authors.affiliation: Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA; Department of Genetics; University of North Carolina-Chapel Hill; Chapel Hill, NC USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Heise
authors.affiliation: Department of Microbiology; School of Medicine; University of Washington; Seattle, WA USA; Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA.
authors.forename: Xinxia
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Microbiology; School of Medicine; University of Washington; Seattle, WA USA; Pacific Northwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research; Portland, OR USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D009980:Influenza A virus / Q000187:drug effects / Q000502:physiology; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058977:Molecular Sequence Annotation; D012327:RNA Virus Infections / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D062085:RNA, Long Noncoding / Q000235:genetics*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects / Q000502:physiology; D017423:Sequence Analysis, RNA
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D062085:RNA, Long Noncoding
keywords: collaborative cross; influenza virus; interferon; long non-coding rna; rna-seq; sars-cov