期刊
SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-26135-9
关键词
-
资金
- National Institutes of Health (NIH) [R35 GM130361]
- Tong Tsung and Wei Fong Chao Foundation [GT007457]
- Chau Hoi Sheun Foundation [GT007457]
The study found that SARS-CoV-2 infection causes global changes in host gene expression and differential expression of many host miRNAs. In addition, an expanded landscape of SARS-CoV-2-derived small viral RNAs (svRNAs) was discovered, which are predicted to interact with differentially expressed host mRNAs and miRNAs. These findings suggest that svRNAs may play a role in the propagation of SARS-CoV-2 and antagonizing them may have therapeutic value.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19) in humans, with symptoms ranging from mild to severe, including fatality. The molecular mechanisms surrounding the effects of viral infection on the host RNA machinery remain poorly characterized. We used a comparative transcriptomics approach to investigate the effects of SARS-CoV-2 infection on the host mRNA and sRNA expression machinery in a human lung epithelial cell line (Calu-3) and an African green monkey kidney cell line (Vero-E6). Upon infection, we observed global changes in host gene expression and differential expression of dozens of host miRNAs, many with known links to viral infection and immune response. Additionally, we discovered an expanded landscape of more than a hundred SARS-CoV-2-derived small viral RNAs (svRNAs) predicted to interact with differentially expressed host mRNAs and miRNAs. svRNAs are derived from distinct regions of the viral genome and sequence signatures suggest they are produced by a non-canonical biogenesis pathway. 52 of the 67 svRNAs identified in Calu-3 cells are predicted to interact with differentially expressed miRNAs, with many svRNAs having multiple targets. Accordingly, we speculate that these svRNAs may play a role in SARS-CoV-2 propagation by modulating post-transcriptional gene regulation, and that methods for antagonizing them may have therapeutic value.
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