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

被引：452

作者：

Li, Jianhua ^{[1
]}

Liu, Kuancheng ^{[1
]}

Liu, Yang ^{[1
]}

Xu, Yan ^{[1
]}

Zhang, Fei ^{[1
]}

Yang, Huijuan ^{[1
]}

Liu, Jiangxia ^{[1
]}

Pan, Tingting ^{[1
]}

Chen, Jieliang ^{[1
]}

Wu, Min ^{[2
]}

Zhou, Xiaohui ^{[3
]}

Yuan, Zhenghong ^{[1
,2
]}

机构：

[1] Fudan Univ, Sch Basic Med Sci, Shanghai Med Coll, Key Lab Med Mol Virol, Shanghai 200433, Peoples R China

[2] Fudan Univ, Res Unit, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China

[3] Fudan Univ, Ctr Lab Anim, Shanghai Publ Hlth Clin Ctr, Shanghai 200433, Peoples R China

来源：

NATURE IMMUNOLOGY | 2013年 / 14卷 / 08期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

HEPATITIS-B-VIRUS; INTERFERON-INDUCED TRANSFER; DENDRITIC CELLS; INTERCELLULAR COMMUNICATION; VIRAL RESISTANCE; INNATE IMMUNITY; INFECTED-CELLS; CHIMERIC MICE; TUMOR-GROWTH; C VIRUS;

D O I：

10.1038/ni.2647

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-alpha (IFN-alpha) induced the transfer of resistance to hepatitis B virus (HBV) from nonpermissive liver nonparenchymal cells (LNPCs) to permissive hepatocytes via exosomes. Exosomes from IFN-alpha-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-alpha to mouse hepatitis virus A59 and adenovirus in mice. Thus, we propose an antiviral mechanism of IFN-alpha activity that involves the induction and intercellular transfer of antiviral molecules via exosomes.

引用

页码：793 / +

页数：13

共 52 条

[1] THE HUMAN LEUKEMIA-CELL LINE, THP-1 - A MULTIFACETED MODEL FOR THE STUDY OF MONOCYTE-MACROPHAGE DIFFERENTIATION [J].

AUWERX, J .

EXPERIENTIA, 1991, 47 (01) :22-31

[2] Acid sphingomyelinase activity triggers microparticle release from glial cells [J].

Bianco, Fabio ;

Perrotta, Cristiana ;

Novellino, Luisa ;

Francolini, Maura ;

Riganti, Loredana ;

Menna, Elisabetta ;

Saglietti, Laura ;

Schuchman, Edward H. ;

Furlan, Roberto ;

Clementi, Emilio ;

Matteoli, Michela ;

Verderio, Claudia .

EMBO JOURNAL, 2009, 28 (08) :1043-1054

[3] INTERFERON-INDUCED TRANSFER OF VIRAL RESISTANCE BETWEEN ANIMAL-CELLS [J].

BLALOCK, JE ;

BARON, S .

NATURE, 1977, 269 (5627) :422-425

[4] Interferons at age 50: past, current and future impact on biomedicine [J].

Borden, Ernest C. ;

Sen, Ganes C. ;

Uze, Gilles ;

Silverman, Robert H. ;

Ransohoff, Richard M. ;

Foster, Graham R. ;

Stark, George R. .

NATURE REVIEWS DRUG DISCOVERY, 2007, 6 (12) :975-990

[5] The innate immune response to hepatitis B virus infection: Implications for pathogenesis and therapy [J].

Chang, Jinhong ;

Block, Timothy M. ;

Guo, Ju-Tao .

ANTIVIRAL RESEARCH, 2012, 96 (03) :405-413

[6] Hepatitis B Virus Polymerase Impairs Interferon-α-Induced STAT Activation Through Inhibition of Importin-α5 and Protein Kinase C-δ [J].

Chen, Jieliang ;

Wu, Min ;

Zhang, Xiaonan ;

Zhang, Wen ;

Zhang, Zhanqing ;

Chen, Lixiang ;

He, Jing ;

Zheng, Ye ;

Chen, Cuncun ;

Wang, Fan ;

Hu, Yunwen ;

Zhou, Xiaohui ;

Wang, Cong ;

Xu, Yang ;

Lu, Mengji ;

Yuan, Zhenghong .

HEPATOLOGY, 2013, 57 (02) :470-482

[7]

Chevaliez Stephane, 2009, V189, P203, DOI 10.1007/978-3-540-79086-0_8

[8] The broad-spectrum antiviral functions of IFIT and IFITM proteins [J].

Diamond, Michael S. ;

Farzan, Michael .

NATURE REVIEWS IMMUNOLOGY, 2013, 13 (01) :46-57

[9] Short-Range Exosomal Transfer of Viral RNA from Infected Cells to Plasmacytoid Dendritic Cells Triggers Innate Immunity [J].

Dreux, Marlene ;

Garaigorta, Urtzi ;

Boyd, Bryan ;

Decembre, Elodie ;

Chung, Josan ;

Whitten-Bauer, Christina ;

Wieland, Stefan ;

Chisari, Francis V. .

CELL HOST & MICROBE, 2012, 12 (04) :558-570

[10] Conditional mouse lung cancer models using adenoviral or lentiviral delivery of Cre recombinase [J].

DuPage, Michel ;

Dooley, Alison L. ;

Jacks, Tyler .

NATURE PROTOCOLS, 2009, 4 (07) :1064-1072

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