MiRNAs: EBV Mechanism for Escaping Host's Immune Response and Supporting Tumorigenesis

Overview

Journal Pathogens

Date 2020 May 14

PMID 32397085

Citations 15

Authors

Snjezana Zidovec Lepej

Maja Matulic

Paula Grskovic

Mirjana Pavlica

Leona Radmanic

Petra Korac

Affiliations

Soon will be listed here.

Abstract

Epstein-Barr virus (EBV) or human herpesvirus 4 (HHV-4) is a ubiquitous human oncogenic virus, and the first human virus found to express microRNAs (miRNAs). Its genome contains two regions encoding more than 40 miRNAs that regulate expression of both viral and human genes. There are numerous evidences that EBV miRNAs impact immune response, affect antigen presentation and recognition, change T- and B-cell communication, drive antibody production during infection, and have a role in cell apoptosis. Moreover, the ability of EBV to induce B-cell transformation and take part in mechanisms of oncogenesis in humans is well known. Although EBV infection is associated with development of various diseases, the role of its miRNAs is still not understood. There is abundant data describing EBV miRNAs in nasopharyngeal carcinoma and several studies that have tried to evaluate their role in gastric carcinoma and lymphoma. This review aims to summarize so far known data about the role of EBV miRNAs in altered regulation of gene expression in human cells in EBV-associated diseases.

Citing Articles

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References

Fink S, Gandhi M, Nourse J, Keane C, Jones K, Crooks P . A comprehensive analysis of the cellular and EBV-specific microRNAome in primary CNS PTLD identifies different patterns among EBV-associated tumors. Am J Transplant. 2014; 14(11):2577-87. DOI: 10.1111/ajt.12858. View

Wang Y, Guo Z, Shu Y, Zhou H, Wang H, Zhang W . BART miRNAs: an unimaginable force in the development of nasopharyngeal carcinoma. Eur J Cancer Prev. 2016; 26(2):144-150. PMC: 5321115. DOI: 10.1097/CEJ.0000000000000221. View

Xia T, OHara A, Araujo I, Barreto J, Carvalho E, Sapucaia J . EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. Cancer Res. 2008; 68(5):1436-42. PMC: 2855641. DOI: 10.1158/0008-5472.CAN-07-5126. View

Imig J, Motsch N, Zhu J, Barth S, Okoniewski M, Reineke T . microRNA profiling in Epstein-Barr virus-associated B-cell lymphoma. Nucleic Acids Res. 2010; 39(5):1880-93. PMC: 3061055. DOI: 10.1093/nar/gkq1043. View

Min K, Lee S . EBV miR-BART10-3p Promotes Cell Proliferation and Migration by Targeting DKK1. Int J Biol Sci. 2019; 15(3):657-667. PMC: 6367590. DOI: 10.7150/ijbs.30099. View

Gilligan K, Rajadurai P, Lin J, Busson P, Abdel-Hamid M, Prasad U . Expression of the Epstein-Barr virus BamHI A fragment in nasopharyngeal carcinoma: evidence for a viral protein expressed in vivo. J Virol. 1991; 65(11):6252-9. PMC: 250325. DOI: 10.1128/JVI.65.11.6252-6259.1991. View

Cai L, Lyu X, Luo W, Cui X, Ye Y, Yuan C . EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN. Oncogene. 2014; 34(17):2156-66. DOI: 10.1038/onc.2014.341. View

Zhou L, Bu Y, Liang Y, Zhang F, Zhang H, Li S . Epstein-Barr Virus (EBV)-BamHI-A Rightward Transcript (BART)-6 and Cellular MicroRNA-142 Synergistically Compromise Immune Defense of Host Cells in EBV-Positive Burkitt Lymphoma. Med Sci Monit. 2016; 22:4114-4120. PMC: 5094474. DOI: 10.12659/msm.897306. View

Skalsky R, Corcoran D, Gottwein E, Frank C, Kang D, Hafner M . The viral and cellular microRNA targetome in lymphoblastoid cell lines. PLoS Pathog. 2012; 8(1):e1002484. PMC: 3266933. DOI: 10.1371/journal.ppat.1002484. View

10.

Chen J, Zhou L, Qiu X, Yang R, Liang J, Pan Y . Determination and genome-wide analysis of Epstein-Barr virus (EBV) sequences in EBV-associated gastric carcinoma from Guangdong, an endemic area of nasopharyngeal carcinoma. J Med Microbiol. 2018; 67(11):1614-1627. DOI: 10.1099/jmm.0.000839. View

11.

Mishra R, Kumar A, Ingle H, Kumar H . The Interplay Between Viral-Derived miRNAs and Host Immunity During Infection. Front Immunol. 2020; 10:3079. PMC: 6989438. DOI: 10.3389/fimmu.2019.03079. View

12.

Zuo L, Yue W, Du S, Xin S, Zhang J, Liu L . An update: Epstein-Barr virus and immune evasion via microRNA regulation. Virol Sin. 2017; 32(3):175-187. PMC: 6702289. DOI: 10.1007/s12250-017-3996-5. View

13.

Pfeffer S, Zavolan M, Grasser F, Chien M, Russo J, Ju J . Identification of virus-encoded microRNAs. Science. 2004; 304(5671):734-6. DOI: 10.1126/science.1096781. View

14.

Zheng X, Wang J, Wei L, Peng Q, Gao Y, Fu Y . Epstein-Barr Virus MicroRNA miR-BART5-3p Inhibits p53 Expression. J Virol. 2018; 92(23). PMC: 6232473. DOI: 10.1128/JVI.01022-18. View

15.

Pope J . Establishment of cell lines from peripheral leucocytes in infectious mononucleosis. Nature. 1967; 216(5117):810-1. DOI: 10.1038/216810a0. View

16.

Huang W, Lin C . EBV-encoded miR-BART20-5p and miR-BART8 inhibit the IFN-γ-STAT1 pathway associated with disease progression in nasal NK-cell lymphoma. Am J Pathol. 2014; 184(4):1185-97. DOI: 10.1016/j.ajpath.2013.12.024. View

17.

Lin C, Zong J, Lin W, Wang M, Xu Y, Zhou R . EBV-miR-BART8-3p induces epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma cells through activating NF-κB and Erk1/2 pathways. J Exp Clin Cancer Res. 2018; 37(1):283. PMC: 6257964. DOI: 10.1186/s13046-018-0953-6. View

18.

Owen K, Brockwell N, Parker B . JAK-STAT Signaling: A Double-Edged Sword of Immune Regulation and Cancer Progression. Cancers (Basel). 2019; 11(12). PMC: 6966445. DOI: 10.3390/cancers11122002. View

19.

Gurer C, Strowig T, Brilot F, Pack M, Trumpfheller C, Arrey F . Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses. Blood. 2008; 112(4):1231-9. PMC: 2515117. DOI: 10.1182/blood-2008-03-148072. View

20.

Skinner C, Ivanov N, Barr S, Chen Y, Skalsky R . An Epstein-Barr Virus MicroRNA Blocks Interleukin-1 (IL-1) Signaling by Targeting IL-1 Receptor 1. J Virol. 2017; 91(21). PMC: 5640834. DOI: 10.1128/JVI.00530-17. View