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Published on: February 28, 2021
Lung-Derived Exosomal miR-483-3p Regulates the Innate Immune Response to Influenza Virus Infection
Tadashi Maemura1,2, Satoshi Fukuyama1, Yukihiko Sugita3
1Division of Virology, Department of Microbiology and Immunology, Japan.
Abstract:
Exosomes regulate cell-cell communication by transferring functional proteins and RNAs between cells. Here, to clarify the function of exosomes during influenza virus infection, we characterized lung-derived exosomal microRNAs (miRNAs). Among the detected miRNAs, miR-483-3p was present at high levels in bronchoalveolar lavage fluid (BALF) exosomes during infection of mice with various strains of influenza virus, and miR-483-3p transfection potentiated gene expression of type I interferon and proinflammatory cytokine upon viral infection of MLE-12 cells. RNF5, a regulator of the RIG-I signaling pathway, was identified as a target gene of miR-483-3p. Moreover, we found that CD81, another miR-483-3p target, functions as a negative regulator of RIG-I signaling in MLE-12 cells. Taken together, this study indicates that BALF exosomal miRNAs may mediate the antiviral and inflammatory response to influenza virus infection.
Insights
Lung-derived exosomes carry microRNAs (miRNAs) that influence influenza virus infection. Specifically, miR-483-3p in bronchoalveolar lavage fluid (BALF) exosomes enhances antiviral responses by targeting RNF5 and CD81, modulating the RIG-I pathway.
Area of Science:
- Molecular Biology
- Immunology
- Virology
Background:
- Exosomes mediate intercellular communication through the transfer of functional molecules.
- Understanding the role of exosomes in viral infections, particularly influenza, is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the function of lung-derived exosomal microRNAs (miRNAs) during influenza virus infection.
- To identify specific miRNAs and their targets involved in the host response to influenza.
Main Methods:
- Characterization of miRNAs within exosomes isolated from bronchoalveolar lavage fluid (BALF) of influenza-infected mice.
- Transfection of miR-483-3p into MLE-12 cells to assess its effect on antiviral gene expression.
- Identification of miR-483-3p target genes using bioinformatics and experimental validation.
Main Results:
- miR-483-3p was significantly upregulated in BALF exosomes during influenza virus infection.
- Transfection of miR-483-3p enhanced type I interferon and proinflammatory cytokine gene expression in response to viral infection.
- RNF5 and CD81 were identified as direct targets of miR-483-3p, and both are involved in regulating the RIG-I signaling pathway.
Conclusions:
- BALF exosomal miRNAs, particularly miR-483-3p, play a significant role in mediating antiviral and inflammatory responses to influenza virus infection.
- miR-483-3p regulates the RIG-I signaling pathway through its targets RNF5 and CD81, contributing to host defense against influenza.
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