4.7 Article

RNA-RNA interactions between SARS-CoV-2 and host benefit viral development and evolution during COVID-19 infection

Journal

BRIEFINGS IN BIOINFORMATICS
Volume 23, Issue 1, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/bib/bbab397

Keywords

COVID-19; miRNA; genomic RNA; RNA-RNA interaction; immune system

Funding

  1. National Natural Science Foundation of China [81971982, 81872798, U1909208]
  2. Key R&D Program of Zhejiang Province [2020003123, 2020003010]
  3. Natural Science Foundation of 18. Zhejiang Province [LR21H300001]
  4. Leading Talent of the 'Ten Thousand Plan' -National High -Level Talents Special Support Plan of China
  5. Fundamental Research Fund for Central Universities [2018QNA7023]
  6. 'Double Top -Class' University Project [181201*194232101]
  7. Alibaba-Zhejiang University Joint Research Center of Future Digital Healthcare
  8. Alibaba Cloud
  9. Information Technology Center of Zhejiang University

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This study demonstrates that the genomic RNA of SARS-CoV-2 can absorb host miRNAs that regulate immune-related genes, suggesting that this may be a crucial mechanism for the virus to survive and develop in the host. By analyzing miRNA datasets and identifying enriched immune-related pathways and protein-protein interactions, the study reveals an imbalance in the host immune response caused by the absorption of SARS-CoV-2 to host miRNAs, with implications for infection and pathogenesis. Additionally, the study finds that the absorption of host miRNAs by SARS-CoV-2 may contribute to the increased infectivity and pathogenicity of certain mutant strains.
Some studies reported that genomic RNA of SARS-CoV-2 can absorb a few host miRNAs that regulate immune-related genes and then deprive their function. In this perspective, we conjecture that the absorption of the SARS-CoV-2 genome to host miRNAs is not a coincidence, which may be an indispensable approach leading to viral survival and development in host. In our study, we collected five datasets of miRNAs that were predicted to interact with the genome of SARS-CoV-2. The targets of these miRNAs in the five groups were consistently enriched immune-related pathways and virus-infectious diseases. Interestingly, the five datasets shared no one miRNA but their targets shared 168 genes. The signaling pathway enrichment of 168 shared targets implied an unbalanced immune response that the most of interleukin signaling pathways and none of the interferon signaling pathways were significantly different. Protein-protein interaction (PPI) network using the shared targets showed that PPI pairs, including IL6-IL6R, were related to the process of SARS-CoV-2 infection and pathogenesis. In addition, we found that SARS-CoV-2 absorption to host miRNA could benefit two popular mutant strains for more infectivity and pathogenicity. Conclusively, our results suggest that genomic RNA absorption to host miRNAs may be a vital approach by which SARS-CoV-2 disturbs the host immune system and infects host cells.

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