SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology

Publication date: Available online 16 February 2017
Source:Cell Host & Microbe
Author(s): Lucía Morales, Juan Carlos Oliveros, Raúl Fernandez-Delgado, Benjamin Robert tenOever, Luis Enjuanes, Isabel Sola
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.

Graphical abstract

Teaser

SARS-CoV causes exacerbated inflammatory responses, extensive lung pathology, and lethal disease in humans. Morales et al. identify SARS-CoV-encoded small viral RNAs (svRNAs) expressed during lung infection. Virus N gene-derived svRNA (svRNA-N) contributes to enhanced lung inflammatory pathology. Antisense svRNA-N inhibitors significantly reduced pulmonary inflammation during in vivo infection in mice.


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