title: SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology.
abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18-22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.
authors.affiliation: Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Madrid, 28049, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Morales
authors.affiliation: Computational Genomics Service, National Center of Biotechnology (CNB-CSIC), Madrid, 28049, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Oliveros
authors.affiliation: Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Madrid, 28049, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Fernandez-Delgado
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Benjamin Robert
authors.initials: BR
authors.lastname: tenOever
authors.affiliation: Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Madrid, 28049, Spain. Electronic address: l.enjuanes@cnb.csic.es.
authors.forename: Luis
authors.initials: L
authors.lastname: Enjuanes
authors.affiliation: Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Madrid, 28049, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sola
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D059014:High-Throughput Nucleotide Sequencing; D008168:Lung / Q000473:pathology*; D051379:Mice; D058727:RNA, Small Untranslated / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000472:pathogenicity*; D045169:Severe Acute Respiratory Syndrome / Q000473:pathology* / Q000821:virology*
chemical_list: D016207:Cytokines; D058727:RNA, Small Untranslated; D012367:RNA, Viral
keywords: SARS-CoV; antagomirs; antiviral; coronavirus; deep sequencing; innate immune response; lung inflammatory pathology; non-coding RNAs; small viral RNAs; virus-host interaction