SARS-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.
Keywords: coronavirus,
SARS-CoV, small viral RNAs, virus-host interaction, lung inflammatory
pathology, antagomirs, deep sequencing, non-coding RNAs, innate immune
response, antiviral
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