Related Experiment Video
Updated: Jul 16, 2026
08:41
Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
miR-29a and miR-15b Modulate SARS-CoV-2 Beta and Omicron Infection in Human Lung Epithelial Cells
Elena Criscuolo1, Nicola Mosca2, Benedetta Giuliani1
1Laboratory of Microbiology and Virology, Vita-Salute San Raffaele University, 20132 Milan, Italy.
International Journal of Molecular Sciences
|July 15, 2026
Summary
Host microRNAs (miRNAs) like miR-29a-3p and miR-15b-5p do not consistently restrict SARS-CoV-2. These miRNAs can paradoxically enhance viral replication, cautioning against miRNA-based antiviral strategies.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Host microRNAs (miRNAs) are investigated as potential innate antiviral mechanisms against SARS-CoV-2.
- Specific miRNAs, miR-29a-3p and miR-15b-5p, are hypothesized to target viral RNA and host factors like Furin and ATG9A.
- Existing functional evidence regarding their antiviral roles is fragmented and contradictory.
Purpose of the Study:
- To functionally assess the antiviral activity of miR-29a-3p and miR-15b-5p against SARS-CoV-2 in human lung epithelial cells.
- To investigate the impact of these miRNAs on viral gene expression, viral RNA levels, and infectious progeny production.
- To determine the effect of miRNA modulation on host factors implicated in viral entry and trafficking.
Main Methods:
- Utilized human Calu-3 lung epithelial cells infected with SARS-CoV-2 Beta and Omicron BA.1 variants.
- Employed parallel gain- and loss-of-function strategies for miR-29a-3p and miR-15b-5p.
- Quantified viral and cellular transcripts via RT-qPCR and measured infectious viral progeny by back-titration on VeroE6/TMPRSS2 cells.
Main Results:
- Both miRNAs transiently suppressed viral gene expression at 6 hours post-infection, followed by a transcript rebound at 24 hours post-infection, particularly for the Omicron variant.
- No significant impact on total extracellular viral RNA was observed.
- Modulation of miR-15b enhanced infectious virus output during Beta variant infection, while miR-29a overexpression boosted Omicron BA.1 infectivity.
- Host factors (Furin, ATG9A, AKT3, TFEB) showed only modest, condition-dependent expression shifts.
Conclusions:
- miR-29a-3p and miR-15b-5p do not act as straightforward antiviral effectors against SARS-CoV-2 in Calu-3 cells.
- These miRNAs function as context-dependent modulators, capable of paradoxically promoting viral replication.
- Findings serve as a cautionary note for the development of miRNA-based antiviral therapeutic strategies against SARS-CoV-2.
