High Levels of miR-483-3p Are Present in Serum Exosomes Upon Infection of Mice With Highly Pathogenic Avian Influenza Virus.

Tadashi Maemura,Satoshi Fukuyama,Yoshihiro Kawaoka

doi:10.3389/fmicb.2020.00144

Abstract

Exosomes, the extracellular vesicles that contain functional proteins and RNAs, regulate cell-cell communication. Recently, our group reported that levels of various microRNAs (miRNAs) in bronchoalveolar lavage fluid exosomes were highly increased in influenza virus-infected mice and that one of those miRNAs, miR-483-3p, was involved in the potentiation of the innate immune responses to influenza virus infection in mouse type II pneumocytes. Here, we evaluated exosomal miR-483-3p levels in the serum of influenza virus-infected mice and found that miR-483-3p levels were significantly increased during infection with a highly pathogenic avian H5N1 influenza virus. Moreover, miR-483-3p-enriched exosomes derived from type II pneumocytes potentiated the expression of proinflammatory cytokine genes in vascular endothelial cells. Our findings suggest that serum exosomal transfer of miR-483-3p might be involved in the inflammatory pathogenesis of H5N1 influenza virus infection.

Highlights

The emergence of highly pathogenic avian influenza (HPAI) viruses has raised serious concerns worldwide
We reported that the miRNA miR-483-3p is involved in the innate immune response to influenza virus infection (Maemura et al, 2018). miR-483-3p was present at high levels in bronchoalveolar lavage fluid (BALF) exosomes in influenza virus-infected mice and potentiated
We investigated the levels of serum exosomal miR-483-3p in influenza virus-infected mice and whether exosomal transfer of miR-483-3p affects the inflammatory response in vascular endothelial cells

Summary

INTRODUCTION

The emergence of highly pathogenic avian influenza (HPAI) viruses has raised serious concerns worldwide. Exosomes are cell-derived extracellular vesicles (30–100 nm in diameter) (Raposo and Stoorvogel, 2013), containing functional proteins, mRNAs, and microRNAs (miRNAs). Because miR-483-3p has been reported to potentiate the activation of the transcription factors IRF3 and NF-κB in MLE-12 cells, we hypothesized that miR-483-3p could potentiate the innate immune response in cells other than lung epithelial cells. It is not known whether miR-483-3p is present in serum exosomes in influenza virusinfected mice and whether miR-483-3p is involved in the immune response in the vascular endothelium during influenza virus infection. We investigated the levels of serum exosomal miR-483-3p in influenza virus-infected mice and whether exosomal transfer of miR-483-3p affects the inflammatory response in vascular endothelial cells

MATERIALS AND METHODS

RESULTS AND DISCUSSION

ETHICS STATEMENT

DISCLOSURES