外泌体在病毒感染诊断和治疗中的作用研究 <sup>*</sup>

doi:10.13523/j.cb.1905040

中国生物工程杂志

2020, Vol. 40

Issue (3): 104-110 DOI: 10.13523/j.cb.1905040

综述

外泌体在病毒感染诊断和治疗中的作用研究 ^*

毛慧,吕玉华,朱丽慧,林月霞(

),廖荣荣(

)

上海市农业科学院畜牧兽医研究所上海 201106

The Role of Exosomes in the Diagnosis and Treatment of Viral Infection

MAO Hui,LV Yu-hua,ZHU Li-hui,LIN Yue-xia(

),LIAO Rong-rong(

)

Institute of Animal Husbandry and Veterinary Sciences, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China

全文: PDF(849 KB) HTML

摘要：

外泌体是多泡体与细胞质膜融合后释放的细胞外囊泡.它们携带有源自分泌细胞的功能性蛋白质,脂质和核酸,能够介导细胞间通信,并在生物体的致病过程中发挥重要作用.当前,对外泌体在病毒感染中的作用机制研究,以及外泌体作为病毒感染诊断和治疗的潜在标志物研究仍处于初级阶段.首先阐述了外泌体的组成和生物学发生机制;然后重点阐述了外泌体在病毒感染中的作用机制,尤其是其在免疫调节中的作用;最后探讨了外泌体作为病毒感染诊断和治疗的潜在标志物的可能性及其应用前景.

关键词： 病毒; 外泌体; 感染; 免疫调节

Abstract:

Exosomes are extracellular vesicles which released upon fusion of multivesicular bodies with the cytoplasmic membrane. Exosomes were shown to contain functional proteins, lipids, and nucleic acids derived from secretory cells that mediating cell-to-cell communications and hence playing important roles in the physiology of the healthy and diseased organism. At present, the investigation on the mechanism of action of exosomes in viral infection and the potential markers of exosomes as a diagnosis and treatment of viral infection are still in their infancy. First described the composition and biogenesis of exosomes, and then focused on the mechanism of action of exosomes in viral infection, especially its role in immune regulation, and finally explored the diagnoses of exomes as a viral infection. And the potential for therapeutic potential markers and their application prospects.

Key words: Virus Exosome Infection Immune regulation

收稿日期: 2019-05-22 出版日期: 2020-04-18

ZTFLH:

Q819

基金资助: *上海市市级农口系统青年人才成长计划[沪农青字(2017)第1-16号];上海市科技兴农项目[沪农科种字(2017)第3-3号];上海市农业科学院青年科技人员助跑计划[ZP173]资助项目

通讯作者: 林月霞,廖荣荣 E-mail: linyuexia@saas.sh.cn;lrrnd@163.com

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引用本文:

毛慧,吕玉华,朱丽慧,林月霞,廖荣荣. 外泌体在病毒感染诊断和治疗中的作用研究 ^*[J]. 中国生物工程杂志, 2020, 40(3): 104-110.

MAO Hui,LV Yu-hua,ZHU Li-hui,LIN Yue-xia,LIAO Rong-rong. The Role of Exosomes in the Diagnosis and Treatment of Viral Infection. China Biotechnology, 2020, 40(3): 104-110.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.1905040 或 https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I3/104

图1 外泌体合成示意图

[1]	Colombo M, Raposo G, Thery C . Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol, 2014,30(1):255-289.
[2]	Wollert T, Hurley J H . Molecular mechanism of multivesicular body biogenesis by escrt complexes. Nature, 2010,464(7290):864-869.
[3]	Colombo M , Moita C, van Niel G, et al. Analysis of escrt functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci, 2013,126(24):5553-5565.
[4]	Schmidt O, Teis D . The escrt machinery. Curr Biol, 2012,22(4):R116-120.
[5]	Maki M, Takahara T, Shibata H . Multifaceted roles of ALG-2 in Ca(2+)-regulated membrane trafficking. Int J Mol Sci, 2016,17(9):E1401.
[6]	Adell M A, Teis D . Assembly and disassembly of the escrt-iii membrane scission complex. FEBS Lett, 2011,585(20):3191-3196.
[7]	Irion U, St Johnston D . Bicoid RNA localization requires specific binding of an endosomal sorting complex. Nature, 2007,445(7127):554-558.
[8]	Zhang J, Li S, Li L , et al. Exosome and exosomal microrna: trafficking, sorting, and function. Genomics Proteomics Bioinformatics, 2015,13(1):17-24.
[9]	Ostrowski M. Carmo N B, Krumeich S , et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol, 2010,12(1):19-30.
[10]	Alonso R, Mazzeo C, Rodriguez M C , et al. Diacylglycerol kinase Α regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of fas ligand-containing exosomes in T lymphocytes. Cell Death Differ, 2011,18(7):1161-1173.
[11]	Alenquer M, Amorim M J . Exosome biogenesis, regulation, and function in viral infection. Viruses, 2015,7(9):5066-5083.
[12]	Ramakrishnaiah V, Thumann C, Fofana I , et al. Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells. Proc Natl Acad Sci USA, 2013,110(32):13109-13113.
[13]	Longatti A, Boyd B, Chisari F V . Virion-independent transfer of replication-competent hepatitis C virus RNA between permissive cells. J Virol, 2015,89(5):2956-2961.
[14]	Madison M N, Okeoma C M . Exosomes: implications in HIV-1 pathogenesis. Viruses, 2015,7(7):4093-4118.
[15]	Eisfeld A J, Kawakami E, Watanabe T , et al. Rab11a is essential for transport of the influenza virus genome to the plasma membrane. J Virol, 2011,85(13):6117-6126.
[16]	Zicari S, Arakelyan A , Palomino R A N, et al. Human cytomegalovirus-infected cells release extracellular vesicles that carry viral surface proteins. Virology, 2018,524(2018):97-105.
[17]	Bello-Morales R, Crespillo A J, Fraile-Ramos A , et al. Role of the small GTPase Rab27a during herpes simplex virus infection of oligodendrocytic cells. BMC Microbiol, 2012,12(1):265-279.
[18]	Villarroya-Beltri C, Gutierrez-Vazquez C, Sanchez-Cabo F , et al. Sumoylated Hnrnpa2b1 controls the sorting of mirnas into exosomes through binding to specific motifs. Nat Commun, 2013,4(1):2980-2990.
[19]	Abd El Gwad A, Matboli M, El-Tawdi A , et al. Role of exosomal competing endogenous RNA in patients with hepatocellular carcinoma. J Cell Biochem, 2018,119(10):8600-8610.
[20]	Feng Z, Hensley L ,McKnight K L, et al . A Pathogenic picornavirus acquires an envelope by Hijacking cellular membranes. Nature, 2013,496(7445):367-371.
[21]	Dreux M, Garaigorta U, Boyd B , et al. Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity. Cell Host Microbe, 2012,12(4):558-570.
[22]	Okamoto M, Oshiumi H, Azuma M , et al. Ips-1 is essential for type Iii Ifn production by hepatocytes and dendritic cells in response to hepatitis C virus infection. J Immunol, 2014,192(6):2770-2777.
[23]	Kouwaki T, Fukushima Y, Daito T , et al. Extracellular vesicles including exosomes regulate innate immune responses to hepatitis B virus infection. Front Immunol, 2016,7:335.
[24]	Baglio S R, van Eijndhoven M A, Koppers-Lalic D , et al. Sensing of latent Ebv infection through exosomal transfer of 5'ppprna. Proc Natl Acad Sci USA, 2016,113(5):587-596.
[25]	Sampey G C, Saifuddin M, Schwab A , et al. Exosomes from HIV-1-infected cells stimulate production of pro-inflammatory cytokines through trans-activating response (Tar) RNA. J Biol Chem, 2016,291(3):1251-1266.
[26]	Nguyen T A, Pang K C, Masters S L . Intercellular communication for innate immunity. Mol Immunol, 2017,86(6):16-22.
[27]	Keryer-Bibens C, Pioche-Durieu C, Villemant C , et al. Exosomes released by Ebv-Infected nasopharyngeal carcinoma cells convey the viral latent membrane protein 1 and the immunomodulatory protein galectin 9. BMC Cancer, 2006,6(1):283-291.
[28]	Rainy N, Zayoud M, Kloog Y , et al. Viral oncomir spreading between B and T cells is employed by kaposi's sarcoma herpesvirus to induce non-cell-autonomous target gene regulation. Oncotarget, 2016,7(27):41870-41884.
[29]	Klibi J ,Nik T i,Riedel A, et al. Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by epstein-barr virus-infected nasopharyngeal carcinoma cells. Blood, 2009,113(9):1957-1966.
[30]	Ansari M A, Singh V V, Dutta S , et al. Constitutive interferon-inducible protein 16-inflammasome activation during epstein-barr virus latency I, Ii, and Iii in B and epithelial cells. J Virol, 2013,87(15):8606-8623.
[31]	Pegtel D M, Cosmopoulos K ,Thorley-Lawson D A, et al. Functional delivery of viral mirnas via exosomes. Proc Natl Acad Sci USA, 2010,107(14):6328-6333.
[32]	Brain O, Owens B M, Pichulik T , et al. The intracellular sensor Nod2 induces microrna-29 expression in human dendritic cells to limit Il-23 release. Immunity, 2013,39(3):521-536.
[33]	Qiu X, Dong S, Qiao F , et al. Hbx-mediated Mir-21 upregulation represses tumor-suppressor function of Pdcd4 in hepatocellular carcinoma. Oncogene, 2013,32(27):3296-3305.
[34]	Baglio S R, van Eijndhoven M A J, Koppers-Lalic D , et al. Sensing of latent EBV infection through exosomal transfer of 5'pppRNA. Proc Natl Acad Sci USA, 2016,113(5):E587-E596.
[35]	Sampey G C, Saifuddin M, Schwab A , et al. Exosomes from HIV-1-infected cells stimulate production of pro-inflammatory cytokines through trans-activating response (TAR) RNA. J Biol Chem, 2016,291(3):1251-1266.
[36]	Ariza M E, Rivailler P, Glaser R , et al. Epstein-Barr virus encoded dUTPase containing exosomes modulate innate and adaptive immune responses in human dendritic cells and peripheral blood mononuclear cells. PLoS One, 2013,8(7):e69827.
[37]	Gutzeit C, Nagy N, Gentile M , et al. Exosomes derived from Burkitt's Lymphoma cell lines induce proliferation, differentiation, and class-switch recombination in B cells. J Immunol, 2014,192(12):5852-5862.
[38]	Siegel R L, Miller K D, Jemal A . Cancer statistics, 2019. CA: A Cancer Journal for Clinicians, 2019,69(1):7-34.
[39]	Cappello F, Logozzi M, Campanella C , et al. Exosome levels in human body fluids: a tumor marker by themselves. Eur J Pharm Sci, 2017,96(1):93-98.
[40]	Yip T T, Ngan R K, Fong A H , et al. Application of circulating plasma/serum Ebv DNA in the clinical management of nasopharyngeal carcinoma. Oral Oncol, 2014,50(6):527-538.
[41]	Zhang G, Zong J, Lin S , et al. Circulating Epstein-Barr virus micrornas Mir-Bart7 and Mir-Bart13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment. Int J Cancer, 2015,136(5):E301-312.
[42]	Zheng X H, Lu L X, Cui C , et al. Epstein-Barr virus Mir-Bart1-5p detection via nasopharyngeal brush sampling is effective for diagnosing nasopharyngeal carcinoma. Oncotarget, 2016,7(4):4972-4980.
[43]	Liu J, Sun H, Wang X , et al. Increased exosomal microrna-21 and microrna-146a levels in the cervicovaginal lavage specimens of patients with cervical cancer. Int J Mol Sci, 2014,15(1):758-773.
[44]	Zhang J, Liu S C, Luo X H , et al. Exosomal long noncoding RNAs are differentially expressed in the cervicovaginal lavage samples of cervical cancer patients. J Clin Lab Anal, 2016,30(6):1116-1121.
[45]	Fan Z, Zhang Q, Chen H , et al. Circulating micrornas as a biomarker to predict therapy efficacy in hepatitis C patients with different genotypes. Microb Pathog, 2017,112(11):320-326.
[46]	Jiao X, Fan Z, Chen H , et al. Serum and exosomal Mir-122 and Mir-199a as a biomarker to predict therapeutic efficacy of hepatitis C patients. J Med Virol, 2017,89(9):1597-1605.
[47]	Gao J, Qiu X, Li X , et al. Expression profiles and clinical value of plasma exosomal Tim-3 and galectin-9 in non-small cell lung cancer. Biochem Biophys Res Commun, 2018,498(3):409-415.
[48]	Cao Y, Yang L, Jiang W , et al. Therapeutic evaluation of Epstein-Barr virus-encoded latent membrane protein-1 targeted dnazyme for treating of nasopharyngeal carcinomas. Mol Ther, 2014,22(2):371-377.
[49]	Daker M, Bhuvanendran S, Ahmad M , et al. Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells. Mol Med Rep, 2013,7(3):731-741.
[50]	Sun D, Zhuang X, Xiang X , et al. A Novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther, 2010,18(9):1606-1614.
[51]	Yang T, Martin P, Fogarty B , et al. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res, 2015,32(6):2003-2014.
[52]	Haney M J, Klyachko N L, Zhao Y , et al. Exosomes as drug delivery vehicles for Parkinson's disease therapy. J Control Release, 2015,207(7):18-30.
[53]	Wahlgren J ,De Karlson L T, Brisslert M , et al. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res, 2012,40(17):e130-e130.
[54]	Ohno S, Takanashi M, Sudo K , et al. Systemically injected exosomes targeted to Egfr deliver antitumor microrna to breast cancer cells. Mol Ther, 2013,21(1):185-191.
[55]	Zhu L, Song H, Zhang X , et al. Inhibition of porcine reproductive and respiratory syndrome virus infection by recombinant adenovirus- and/or exosome-delivered the artificial micrornas targeting sialoadhesin and Cd163 receptors. Virol J, 2014,11(1):225-234.
[56]	Liu F, Du Y, Feng W H . New perspective of host micrornas in the control of Prrsv infection. Vet Microbiol, 2017,209(9):48-56.

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