Cell Host and Microbes
Volume 21, Issue 3, 8 March 2017, Pages 344-355
Lucía Morales, Juan Carlos Oliveros, Raúl Fernandez-Delgado, Benjamin Robertten Oever, Luis Enjuanes, and Isabel Sola
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.
Keywords
coronavirus, SARS-CoV, small viral RNAs, virus-host interaction, lung inflammatory pathology, antagomirs, deep sequencing, non-coding RNAs, innate immune response, antiviral