Lung-Derived Exosomal miR-483-3p Regulates the Innate Immune Response to Influenza Virus Infection

• Published in: The Journal of infectious diseases Vol. 217; no. 9; pp. 1372 - 1382
• Main Authors: Maemura, Tadashi, Fukuyama, Satoshi, Sugita, Yukihiko, Lopes, Tiago J S, Nakao, Tomomi, Noda, Takeshi, Kawaoka, Yoshihiro
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 11.04.2018
• Subjects: Animals; Bronchoalveolar Lavage Fluid; Cell Line; Female; Gene Expression Regulation - immunology; Immunity, Innate - physiology; Lung - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; NF-kappa B; Orthomyxoviridae - immunology; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - virology; Tetraspanin 28 - genetics; Tetraspanin 28 - metabolism; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; influenza virus; microRNA; innate immunity; exosome
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiy035

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. miR-483-3p was present at high levels in bronchoalveolar lavage fluid (BALF) exosome in influenza virus–infected mice. miR-483-3p potentiated innate immune response by suppressing negative regulators of RIG-I signaling. BALF exosomal microRNAs may mediate the immune response to influenza virus infection.