biostudies-literature00440Morales LEuropean Zoonoses anticipation and preparedness initiativeNIAID NIH HHSMinistry of Science and Innovation of SpainMinistry of Science an Innovation of SpainNIH344-355https://www.ebi.ac.uk/biostudies/studies/S-EPMC5662013biostudies-literatureUnknown21(3)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.Cell host & microbeSARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology.PMC5662013BIO2013-42869-RHHSN266200700010CBIO2016-75549-R AEI/FEDER, UE0258-3413/HHSN266200700010CBIO2010-167052P01AI060699IMI_JU_115760P01 AI060699Morales LtenOever BRFernandez-Delgado ROliveros JCEnjuanes LSola I44falseSARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology.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.2017-01-01T00:00:00Z2017 Mar2024-12-04T12:46:18.519Z2019-03-27T03:00:19ZS-EPMC56620132821625110.1016/j.chom.2017.01.015