Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity

• Published in: Nature immunology Vol. 14; no. 8; pp. 793 - 803
• Main Authors: Li, Jianhua, Liu, Kuancheng, Liu, Yang, Xu, Yan, Zhang, Fei, Yang, Huijuan, Liu, Jiangxia, Pan, Tingting, Chen, Jieliang, Wu, Min, Zhou, Xiaohui, Yuan, Zhenghong
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2013; Nature Publishing Group
• Subjects: 631/250/262; Adenovirus; Analysis; Animals; Biomedicine; Care and treatment; Exosomes - immunology; Exosomes - virology; Health aspects; Hep G2 Cells; Hepatitis B - drug therapy; Hepatitis B - immunology; Hepatitis B virus; Hepatitis B virus - immunology; Humans; Immunoblotting; Immunology; Infectious Diseases; Influence; Interferon; Interferon-alpha - pharmacology; Liver - immunology; Liver - virology; Lysosomes; Mice; Murine hepatitis virus; Signal Transduction - immunology; Virus Replication - immunology; China
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.2647

Exosomes have diverse physiological roles. Yuan and colleagues show that packaging of antiviral molecules into exosomes, followed by their release, is important in resistance to hepatitis viruses. The cell-to-cell transmission of viral resistance is a potential mechanism for amplifying the interferon-induced antiviral response. In this study, we report that interferon-α (IFN-α) induced the transfer of resistance to hepatitis B virus (HBV) from nonpermissive liver nonparenchymal cells (LNPCs) to permissive hepatocytes via exosomes. Exosomes from IFN-α-treated LNPCs were rich in molecules with antiviral activity. Moreover, exosomes from LNPCs were internalized by hepatocytes, which mediated the intercellular transfer of antiviral molecules. Finally, we found that exosomes also contributed to the antiviral response of IFN-α to mouse hepatitis virus A59 and adenovirus in mice. Thus, we propose an antiviral mechanism of IFN-α activity that involves the induction and intercellular transfer of antiviral molecules via exosomes.