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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Problems of Virology</journal-id><journal-title-group><journal-title xml:lang="en">Problems of Virology</journal-title><trans-title-group xml:lang="ru"><trans-title>Вопросы вирусологии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0507-4088</issn><issn publication-format="electronic">2411-2097</issn><publisher><publisher-name xml:lang="en">Central Research Institute for Epidemiology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">403</article-id><article-id pub-id-type="doi">10.36233/0507-4088-2020-65-4-191-202</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Epstein-Barr virus (<italic>Herpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Human gammaherpesvirus 4</italic>): replication strategies</article-title><trans-title-group xml:lang="ru"><trans-title>Вирус Эпштейна-Барр (<italic>Herpesviridae: Gammaherpesvirinae: Lymphocryptovirus: Human gammaherpesvirus 4</italic>): репликативные стратегии</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0507-0174</contrib-id><name-alternatives><name xml:lang="en"><surname>Yakushina</surname><given-names>S. A.</given-names></name><name xml:lang="ru"><surname>Якушина</surname><given-names>С. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Sofia A. Yakushina - junior researcher of the Laboratory of Chronic Viral Infections.</p><p>18 Gamaleya St, Moscow, 123098</p></bio><bio xml:lang="ru"><p>Якушина Софья Александровна – младший научный сотрудник лаборатории хронических вирусных инфекций.</p><p>123098, Москва, ул. Гамалеи, д. 18</p></bio><email>sofia.iakushina@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7336-409X</contrib-id><name-alternatives><name xml:lang="en"><surname>Kisteneva</surname><given-names>L. B.</given-names></name><name xml:lang="ru"><surname>Кистенева</surname><given-names>Л. Б.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Lidiya B. Kisteneva - Doct. Sci. (Med.), Head of the Laboratory of Chronic Viral Infections.</p><p>18 Gamaleya St, Moscow, 123098</p></bio><bio xml:lang="ru"><p>Кистенева Лидия Борисовна – доктор медицинских наук, зав. лабораторией хронических вирусных инфекций.</p><p>123098, Москва, ул. Гамалеи, д. 18</p></bio><email>lidia.kisteneva@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of Russian Federation</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный исследовательский центр эпидемиологии и микробиологии имени почётного академика Н.Ф. Гамалеи» Минздрава России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2020-09-17" publication-format="electronic"><day>17</day><month>09</month><year>2020</year></pub-date><volume>65</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>191</fpage><lpage>202</lpage><history><date date-type="received" iso-8601-date="2020-09-16"><day>16</day><month>09</month><year>2020</year></date><date date-type="accepted" iso-8601-date="2020-09-16"><day>16</day><month>09</month><year>2020</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2020, Yakushina S.A., Kisteneva L.B.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2020, Якушина С.А., Кистенева Л.Б.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="en">Yakushina S.A., Kisteneva L.B.</copyright-holder><copyright-holder xml:lang="ru">Якушина С.А., Кистенева Л.Б.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://virusjour.crie.ru/jour/article/view/403">https://virusjour.crie.ru/jour/article/view/403</self-uri><abstract xml:lang="en"><p>The Epstein-Barr virus (EBV), one of the most common in the human population, is capable of lifelong persistence in resting memory B-cells, in T-cells in case of type 2 EBV, and in some undifferentiated epithelial cells. In most people, EBV persistence is not accompanied by significant symptoms, but frequent virus activations are associated with the increased risks of severe diseases, such as chronic active Epstein-Barr virus infection, hemophagocytic lymphohistiocytosis, multiple sclerosis, systemic lupus erythematosus, gastric and nasopharyngeal carcinomas, and a variety of T- and B-cell lymphomas. Therefore, the molecular viral and host cell processes during asymptomatic or low-symptom EBV persistence are of great interest. This review describes the behavior of the viral DNA in an infected cell and the forms of its existence (linear, circular episome, chromosomally integrated forms), as well as methods of EBV genome copying. Two closely related cycles of viral reproduction are considered. Lytic activation is unfavorable for the survival of a particular viral genome in the cell, and may be a result of differentiation of a latently infected cell, or the arrival of stress signals due to adverse extracellular conditions. The EBV has a large number of adaptive mechanisms for limiting lytic reactivation and reducing hostility of host immune cells. Understanding the molecular aspects of EBV persistence will help in the future develop more effective targeted drugs for the treatment of both viral infection and associated diseases.</p></abstract><trans-abstract xml:lang="ru"><p>Вирус Эпштейна-Барр (ВЭБ) - один из наиболее распространённых в человеческой популяции, он способен на протяжении всей жизни персистировать в покоящихся В-клетках памяти, в Т-клетках (ВЭБ 2-го типа) и в некоторых недифференцированных эпителиальных клетках. У большинства людей персистенция ВЭБ не сопровождается значительными симптомами, но при частых активациях вируса возрастают риски тяжёлых сопутствующих заболеваний, включая хроническую активную ВЭБ-инфекцию, гемофагоцитарный лимфогистиоцитоз, рассеянный склероз, системную красную волчанку, карциному желудка и носоглотки, а также различные Т- и В-клеточные лимфомы. Большой интерес представляют молекулярные вирусные и клеточные процессы во время бессимптомной или малосимптомной персистенции ВЭБ. В этом обзоре рассматриваются поведение вирусной ДНК в заражённой клетке, формы её существования (линейная, циркулярная эписома, хромосомно-интегрированная форма), а также методы копирования генома ВЭБ. Рассмотрены два тесно связанных цикла вируса - литический и латентный. Литическая активация неблагоприятна для выживания конкретного вирусного генома в клетке, она запускается в результате дифференцировки латентно инфицированной клетки или появления стресс-сигналов из-за неблагоприятных условий внеклеточной среды. ВЭБ обладает большим количеством адаптивных механизмов для предотвращения литической реактивации и снижения враждебности иммунных клеток хозяина. Понимание молекулярных аспектов персистенции ВЭБ поможет в будущем разработать более эффективные, таргетные препараты для лечения как самой вирусной инфекции, так и сопутствующих заболеваний.</p></trans-abstract><kwd-group xml:lang="en"><kwd>persistence</kwd><kwd>Epstein-Barr virus</kwd><kwd>viral replication</kwd><kwd>episome</kwd><kwd>chromosomal integration</kwd><kwd>activation</kwd><kwd>latency</kwd><kwd>DNA</kwd><kwd>RNA</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>персистенция</kwd><kwd>вирус Эпштейна-Барр</kwd><kwd>вирусная репликация</kwd><kwd>эписома</kwd><kwd>хромосомная интеграция</kwd><kwd>активация</kwd><kwd>латентность</kwd><kwd>ДНК</kwd><kwd>РНК</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>1.	Kieff E. Epstein-Barr virus and its replication. In: Fields B.N., Knipe D.M., Howley P.M., eds. Field’s virology. Volume 2. Philadelphia: Lippincott-Raven Publishers; 1996: 2343-96.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>2.	Бошьян Р.Е. Инфекция, вызванная вирусом Эпштейна-Барр: эпидемиологические проявления и лабораторная диагностика: Автореф. дисс... канд. мед. наук. М.; 2009.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>3.	Hutt-Fletcher LM. Epstein-Barr virus entry. J. Virol. 2007; 81(15): 7825-32. DOI: http://doi.org/10.1128/JVI.00445-07</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>4.	Fearon D.T., Carter R.H. The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annu. Rev. Immunol. 1995; 13: 127-49. DOI: http://doi.org/10.1146/annurev.iy.13.040195.001015</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>5.	Fingeroth J.D., Diamond M.E., Sage D.R., Hayman J., Yates J.L. CD21-Dependent infection of an epithelial cell line, 293, by Epstein-Barr virus. J. Virol. 1999; 73(3): 2115-25. DOI: http://doi.org/10.1128/JVI.73.3.2115-2125.1999</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>6.	Maruo S., Yang L., Takada K. Roles of Epstein-Barr virus glycoproteins gp350 and gp25 in the infection of human epithelial cells. J. Gen. Virol. 2001; 82(Pt. 10): 2373-83. DOI: http://doi.org/10.1099/0022-1317-82-10-2373</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>7.	Xiao J., Palefsky J.M., Herrera R., Berline J., Tugizov S.M. EBV BMRF-2 facilitates cell-to-cell spread of virus within polarized oral epithelial cells. Virology. 2009; 388(2): 335-43. DOI: http://doi.org/10.1016/j.virol.2009.03.030</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>8.	Rickinson A.B., Kieff E. Epstein-Barr virus. In: Fields B.N., Knipe D.M., Howley P.M., eds. Field’s virology. Volume 2. Philadelphia: Lippincott-Raven Publishers; 2007: 2655-700.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>9.	Souza T.A., Stollar B.D., Sullivan J.L., Luzuriaga K., Thorley-Law-son D.A. Peripheral B cells latently infected with Epstein-Barr virus display molecular hallmarks of classical antigen-selected memory B cells. Proc. Natl. Acad. Sci. USA. 2005; 102(50): 18093-8. DOI: http://doi.org/10.1073/pnas.0509311102</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>10.	Thorley-Lawson D.A. EBV persistence - introducing the virus. Curr. Top. Microbiol. Immunol. 2015; 390(Pt. 1): 151-209. DOI: http://doi.org/10.1007/978-3-319-22822-8_8</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>11.	Hochberg D., Souza T., Catalina M., Sullivan J.L., Luzuriaga K., Thorley-Lawson D.A. Acute infection with Epstein-Barr Virus targets and overwhelms the peripheral memory B-cell compartment with resting, latently infected cells. J. Virol. 2004; 78(10): 5194-204. DOI: http://doi.org/rn.n28/JVI.78.rn.5194-5204.2004</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>12.	Coleman C.B., Wohlford E.M., Smith N.A., King C.A., Ritchie J.A., Baresel P.C., et al. Epstein-Barr virus type 2 latently infects T-cells, inducing an atypical activation characterized by expression of lymphotactic cytokines. J. Virol. 2015; 89(4): 2301-12. DOI: http://doi.org/10.1128/JVI.03001-14</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>13.	Якушина С.А., Кистенева Л.Б. Влияние персистенции вируса Эпштейна-Барр на развитие иммуноопосредованных соматических заболеваний. Российский вестник перинатологии и педиатрии. 2018; 63(1): 22-7. DOI: http://doi.org/10.21508/1027-4065-2018-63-1-22-27</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>14.	Loebel M., Eckey M., Sotzny F., Hahn E., Bauer S., Grabowski P., et al. Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray. PLoS One. 2017; 12(6): e0179124. DOI: http://doi.org/10.1371/journal.pone.0179124</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>15.	Handel A.E., Williamson A.J., Disanto G., Handunnetthi L., Giovannoni G., Ramagopalan S.V. An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One. 2010; 5(9): e12496. DOI: http://doi.org/10.1371/journal.pone.0012496</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>16.	Draborg A.H., Duus K., Houen G. Epstein-Barr virus in systemic autoimmune diseases. Clin. Dev. Immunol. 2013; 2013: 535738. DOI: http://doi.org/10.1155/2013/535738</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>17.	McGeoch D.J., Gatherer D. Lineage structures in the genome sequences of three Epstein-Barr virus strains. Virology. 2007; 359(1): 1-5. DOI: http://doi.org/10.1016/j.virol.2006.10.009</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>18.	Kanda T., Yajima M., Ikuta K. Epstein-Barr virus strain variation and cancer. CancerSci. 2019;110(4): 1132-9. DOI: http://doi.org/10.1111/cas.13954</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>19.	Zeng M.S., Li D.J., Liu Q.L., Song L.B., Li M.Z., Zhang R.H., et al. Genomic sequence analysis of Epstein-Barr virus strain GD1 from a nasopharyngeal carcinoma patient. J. Virol. 2005; 79(24): 15323-30. DOI: http://doi.org/10.1128/JVI.79.24.15323-15330.2005</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>20.	Tsai M.H., Lin X., Shumilov A., Bernhardt K., Feederle R., Poirey R., et al. The biological properties of different Epstein-Barr virus strains explain their association with various types of cancers. On-cotarget. 2016; 8(6): 10238-54. DOI: http://doi.org/10.18632/oncotarget.14380</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>21.	Lin Z., Wang X., Strong M.J., Concha M., Baddoo M., Xu G., et al. Whole-genome sequencing of the Akata and Mutu Epstein-Barr virus strains. J. Virol. 2013; 87(2): 1172-82. DOI: http://doi.org/10.1128/JVI.02517-12</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>22.	Palser A.L., Grayson N.E., White R.E., Corton C., Correia S., Ba Abdullah M.M., et al. Genome diversity of Epstein-Barr virus from multiple tumor types and normal infection. J. Virol. 2015; 89(10): 5222-37. DOI: http://doi.org/10.1128/JVI.03614-14</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>23.	Correia S., Bridges R., Wegner F., Venturini C., Palser A., Middeldorp J.M., et al. Sequence variation of Epstein-Barr Virus: viral types, geography, codon usage, and diseases. J. Virol. 2018; 92(22): e01132-18. DOI: http://doi.org/10.1128/JVI.01132-18</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>24.	Neves M., Marinho-Dias J., Ribeiro J., Sousa H. Epstein-Barr virus strains and variations: Geographic or disease-specific variants? J. Med. Virol. 2017; 89(3): 373-87. DOI: http://doi.org/10.1002/jmv.24633</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>25.	Adamson A.L., Darr D., Holley-Guthrie E., Johnson R.A., Mauser A., Swenson J., et al. Epstein-Barr virus immediate-early proteins BZLF1 and BRLF1 activate the ATF2 transcription factor by increasing the levels of phosphorylated p38 and c-Jun N-terminal kinases. J. Virol. 2000; 74(3): 1224-33. DOI: http://doi.org/10.1128/jvi.74.3.1224-1233.2000</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>26.	Abbott R.J., Quinn L.L., Leese A.M., Scholes H.M., Pachnio A., Rickinson A.B. CD8+ T cell responses to lytic EBV infection: late antigen specificities as subdominant components of the total response. J. Immunol. 2013; 191(11): 5398-409. DOI: http://doi. org/10.4049/jimmunol.1301629</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>27.	Kanegane H., Wakiguchi H., Kanegane C., Kurashige T., Tosato G. Viral interleukin-10 in chronic active Epstein-Barr virus infection. J. Infect. Dis. 1997; 176(1): 254-7. DOI: http://doi.org/10.1086/517260</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>28.	Kang M.S., Kieff E. Epstein-Barr virus latent genes. Exp. Mol. Med. 2015; 47(1): e131. DOI: http://doi.org/10.1038/emm.2014.84</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>29.	Niedobitek G., Agathanggelou A., Herbst H., Whitehead L., Wright D.H., Young L.S. Epstein-Barr virus (EBV) infection in infectious mononucleosis: virus latency, replication and phenotype of EBV-infected cells. J. Pathol. 1997; 182: 151-9. DOI: http://doi.org/10.1002/(SICI)1096-9896(199706)182:2&lt;151::AID-PATH824&gt;3.0.CO;2-3</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>30.	Niedobitek G., Kremmer E., Herbst H., Whitehead L., Dawson C.W., Niedobitek E., et al. Immunohistochemical detection of the Epstein-Barr virus-encoded latent membrane protein 2A in Hodgkin’s disease and infectious mononucleosis. Blood. 1997; 90(4): 1664-72.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>31.	Gulley M.L., Raab-Traub N. Detection of Epstein-Barr virus in human tissues by molecular genetic techniques. Arch. Pathol. Lab. Med. 1993; 117(11): 1115-20.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>32.	Arvin A., Campadelli-Fiume G., Mocarski E., Moore P.S., Roizman B., Whitley R., et al., eds. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge; 2007.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>33.	Hurley E.A., Thorley-Lawson D.A. B cell activation and the establishment ofEpstein-Barr virus latency. J. Exp. Med. 1988; 168(6): 2059-75. DOI: http://doi.org/10.1084/jem.168.6.2059</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>34.	Yates J.L Epstein-Barr virus DNA replication. In: DePamphilis M.	L., ed. DNA Replication in Eukaryotic Cells. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1996: 751-74.</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>35.	Hammerschmidt W., Sugden B. Replication of Epstein-Barr viral DNA. Cold Spring Harb. Perspect. Biol. 2013; 5(1): a013029. DOI: http://doi.org/10.1101/cshperspect.a013029</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>36.	Hammerschmidt W., Sugden B. Identification and characterization of oriLyt, a lytic origin of DNA replication of Epstein-Barr virus. Cell. 1988; 55(3): 427-33. DOI: http://doi.org/10.1016/0092-8674(88)90028-1</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>37.	Neuhierl B., Delecluse H.J. The Epstein-Barr virus BMRF1 gene is essential for lytic virus replication. J. Virol. 2006; 80(10): 5078-81. DOI: http://doi.org/10.1128/JVI.80.10.5078-5081.2006</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>38.	Narita Y., Sugimoto A., Kawashima D., Watanabe T., Kanda T., Ki-mura H., et al. A herpesvirus specific motif of Epstein-Barr virus DNA polymerase is required for the efficient lytic genome synthesis. Sci. Rep. 2015; 5: 11767. DOI: http://doi.org/10.1038/srep11767</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>39.	Schildgen O., Graper S., Blumel J., Matz B. Genome replication and progeny virion production of herpes simplex virus type 1 mutants with temperature-sensitive lesions in the origin-binding protein. J. Virol. 2005; 79(11): 7273-8. DOI: http://doi.org/10.1128/JVI.79.11.7273-7278.2005</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>40.	Daikoku T., Kudoh A., Fujita M., Sugaya Y., Isomura H., Shirata N.	, et al. Architecture of replication compartments formed during Epstein-Barr virus lytic replication. J. Virol. 2005; 79(6): 3409-18. DOI: http://doi.org/10.1128/JVI.79.63409-3418.2005</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>41.	Tsurumi T., Fujita M., Kudoh A. Latent and lytic Epstein-Barr virus replication strategies. Rev. Med. Virol. 2005; 15(1): 3-15. dOi: http://doi.org/10.1002/rmv.441</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>42.	Maul G.G. Nuclear domain 10, the site of DNA virus transcription and replication. Bioessays. 1998; 20(8): 660-7. DOI: http://doi.org/10.1002/(SICI)1521-1878(199808)20:8&lt;660::AID-BIES9&gt;3.0.CO;2-M</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>43.	Rivera-Molina Y.A., Martinez F.P., Tang Q. Nuclear domain 10 of the viral aspect. World J. Virol. 2013; 2(3): 110-22. DOI: http://doi.org/10.5501/wjv.v2.i3.110</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>44.	Amon W., White R.E., Farrell P.J. Epstein-Barr virus origin of lytic replication mediates association of replicating episomes with promyelocytic leukaemia protein nuclear bodies and replication compartments. J. Gen. Virol. 2006; 87(Pt. 5): 1133-7. DOI: http://doi.org/10.1099/vir.0.81589-0</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>45.	Sivachandran N., Wang X., Frappier L. Functions of the Epstein-Barr Virus EBNA1 Protein in Viral Reactivation and Lytic Infection. J. Virol. 2012; 86(11): 6146-58. DOI: http://doi.org/10.1128/JVI.00013-12</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>46.	Ling P.D., Peng R.S., Nakajima A., Yu J.H., Tan J., Moses S.M., et al. Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100. EMBO J. 2005; 24: 3565-75. DOI: http://doi.org/10.1038/sj.emboj.7600820</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>47.	Tsai K., Thikmyanova N., Wojcechowskyj J.A., Delecluse H.J., Lieberman P.M. EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. PLoSPathog. 2011; 7(11): e1002376. DOI: http://doi.org/10.1371/journal.ppat.1002376</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>48.	Shaw J.E., Levinger L.F., Carter C.W. Nucleosomal structure of Epstein-Barr virus DNA in transformed cell lines. J. Virol. 1979; 29(2): 657-65. DOI: http://doi.org/10.1128/JVI.29.2.657-665.1979</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>49.	Morissette G., Flamand L. Herpesviruses and chromosomal integration. J. Virol. 2010; 84(23): 12100-9. DOI: http://doi.org/10.n28/JVI.01169-m</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>50.	Reisinger J., Rumpler S., Lion T., Ambros P.F. Visualization of ep-isomal and integrated Epstein-Barr virus DNA by fiber fluorescence in situ hybridization. Int. J. Cancer. 2006; 118(7): 1603-8. DOI: http://doi.org/10.1002/ijc.21498</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>51.	Nanbo A., Sugden A., Sugden B. The coupling of synthesis and partitioning of EBV’s plasmid replicon is revealed in live cells. EMBO J. 2007; 26(19): 4252-62. DOI: http://doi.org/10.1038/sj.emboj.7601853</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>52.	Humme S., Reisbach G., Feederle R., Delecluse H.J., Bousset K., Hammerschmidt W., et al. The EBV nuclear antigen 1 (EBNA1) enhances B cell immortalization several thousandfold. Proc. Natl. Acad. Sci. USA. 2003; 100(19): 10989-94. DOI: http://doi.org/10.1073/pnas.1832776100</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>53.	Bell P., Lieberman P.M., Maul G.G. Lytic but not latent replication of Epstein-Barr virus is associated with PML and induces sequential release of nuclear domain 10 proteins. J. Virol. 2000; 74(24): 11800-10. DOI: http://doi.org/10.1128/jvi.74.24.11800-11810.2000</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>54.	Yates J.L., Guan N. Epstein-Barr virus-derived plasmids replicate only once per cell cycle and are not amplified after entry into cells. J. Virol. 1991; 65(1): 483-8. DOI: http://doi.org/10.1128/JVI.65.1.483-488.1991</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>55.	Gahn T.A., Schildkraut C.L. The Epstein-Barr virus origin of plasmid replication, oriP, contains both the initiation and termination sites of DNA replication. Cell. 1989; 58(3): 527-35. DOI: http://doi.org/10.1016/0092-8674(89)90433-9</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>56.	Deng Z., Lezina L., Chen C.J., Shtivelband S., So W., Lieberman P.M. Telomeric proteins regulate episomal maintenance of Epstein-Barr virus origin of plasmid replication. Mol. Cell. 2002; 9(3): 493-503. DOI: http://doi.org/10.1016/s1097-2765(02)00476-8</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>57.	Rawlins D.R., Milman G., Hayward S.D., Hayward G.S. Sequence-specific DNA binding of the Epstein-Barr virus nuclear antigen (EBNA-1) to clustered sites in the plasmid maintenance region. Cell. 1985; 42(3): 859-68. DOI: http://doi.org/10.1016/0092-8674(85)90282-x</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>58.	Yates J.L., Camiolo S.M., Bashaw J.M. The minimal replicator of Epstein-Barr virus oriP. J. Virol. 2000; 74(10): 4512-22. DOI: http://doi.org/10.1128/jvi.74.10.4512-4522.2000</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>59.	Norio P., Schildkraut C.L. Plasticity of DNA replication initiation in Epstein-Barr virus episomes. PLoSBiology. 2004;2(6): e152. DOI: http://doi.org/10.1371/journal.pbio.0020152</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>60.	Norio P., Schildkraut C.L., Yates J.L. Initiation of DNA replication within oriP is dispensable for stable replication of the latent Ep-stein-barr virus chromosome after infection of established cell lines. J. Virol. 2000; 74(18): 8563-74. DOI: http://doi.org/10.1128/jvi.74.18.8563-8574.2000</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>61.	Wang C.Y., Sugden B. Identifying a property of origins of DNA synthesis required to support plasmids stably in human cells. Proc. Natl. Acad. Sci. USA. 2008; 105(28): 9639-44. DOI: http://doi.org/10.1073/pnas.0801378105</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>62.	Zhou J., Snyder A.R., Lieberman P.M. Epstein-Barr virus episome stability is coupled to a delay in replication timing. J. Virol. 2009; 83(5): 2154-62. DOI: http://doi.org/10.1128/JVI.02115-08</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>63.	Chang Y., Cheng S.D., Tsai C.H. Chromosomal integration of Ep-stein-Barr virus genomes in nasopharyngeal carcinoma cells. Head Neck. 2002; 24(2): 143-50. DOI: http://doi.org/10.1002/hed.10039</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>64.	Epstein M.A., Achong B.G., Barr Y.M., Zajac B., Henle G., Henle W. Morphological and virological investigations on cultured Burkitt tumor lymphoblasts (strain Raji). J. Natl. Cancer Inst. 1966; 37(4): 547-59.</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>65.	Cheung S.T., Huang D.P., Hui A.B., Lo K.W., Ko C.W., Tsang Y.S., et al. Nasopharyngeal carcinoma cell line (C666-1) consistently harbouring Epstein-Barr virus. Int. J. Cancer. 1999; 83(1): 121-6. DOI: http://doi.org/10.1002/(sici)1097-0215(19990924)83:1&lt;121::aid-ijc21&gt;3.0.co;2-f</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>66.	Delecluse H.J., Bartnizke S., Hammerschmidt W., Bullerdiek J., Bornkamm G.W. Episomal and integrated copies of Epstein-Barr virus coexist in Burkitt lymphoma cell lines. J. Virol. 1993; 67(3): 1292-9. DOI: http://doi.org/10.1128/JVI.67.3.1292-1299.1993</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>67.	Traylen C.M., Patel H.R., Fondaw W., Mahatme S., Williams J.F., Walker L.R., et al. Virus reactivation: a panoramic view in human infections. Future Virol. 2011; 6(4): 451-63. DOI: http://doi.org/10.2217/fvl.11.21</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>68.	Gao J., Luo X., Tang K., Li X., Li G. Epstein-Barr virus integrates frequently into chromosome 4q, 2q, 1q and 7q of Burkitt’s lymphoma cell line (Raji). J. Virol. Methods. 2006; 136(1-2): 193-9. DOI: http://doi.org/10.1016/jjviromet.2006.05.013</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>69.	Xiao K., Yu Z., Li X., Li X., Tang K., Tu C., et al. Genome-wide analysis of Epstein-Barr virus (EBV) integration and strain in C666-1 and Raji cells. J. Cancer. 2016; 7(2): 214-24. DOI: http://doi.org/10.7150/jca.13150</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>70.	Takakuwa T., Luo W.J., Ham M.F., Sakane-Ishikawa F., Wada N., Aozasa K. Integration of Epstein-Barr virus into chromosome 6q15 of Burkitt lymphoma cell line (Raji) induces loss of BACH2 expression. Am. J. Pathol. 2004; 164(3): 967-74. DOI: http://doi.org/10.1016/S0002-9440(10)63184-7</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>71.	Xu M., Zhang W.L., Zhu Q., Zhang S., Yao Y.Y., Xiang T., et al. Genome-wide profiling of Epstein-Barr virus integration by targeted sequencing in Epstein-Barr virus associated malignancies. Thera-nostics. 2019; 9(4): 1115-24. DOI: http://doi.org/10.7150/thno.29622</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>72.	Rose C., Green M., Webber S., Kingsley L., Day R., Watkins S., et al. Detection of Epstein-Barr virus genomes in peripheral blood B cells from solid-organ transplant recipients by fluorescence in situ hybridization. J. Clin. Microbiol. 2002; 40(7): 2533-44. DOI: http://doi.org/10.1128/JCM.40.7.2533-2544.2002</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>73.	Hall C.B., Caserta M.T., Schnabel K., Shelley L.M., Marino A.S., Carnahan J.A., et al. Chromosomal integration of human herpesvirus 6 is the major mode of congenital human herpesvirus 6 infection. Pediatrics. 2008; 122(3): 513-20. DOI: http://doi.org/10.1542/peds.2007-2838</mixed-citation></ref></ref-list></back></article>
