Novel replisome-associated proteins at cellular replication forks in EBV-transformed B lymphocytes

English version

Autoři: Huanzhou Xu ^aff001; Ramon D. Perez ^aff002; Tiffany R. Frey ^aff001; Eric M. Burton ^aff001; Sudha Mannemuddhu ^aff003; John D. Haley ^aff004; Michael T. McIntosh ^aff005; Sumita Bhaduri-McIntosh ^aff006
Působiště autorů: Division of Infectious Disease, Department of Pediatrics, University of Florida, Gainesville, Florida, United States of America ^aff001; Department of Microbiology and Immunology, Stony Brook University, Stony Brook, New Yordk, Unites States of America ^aff002; Division of Nephrology, Dept. of Pediatrics, University of Florida, Gainesville, Florida, United States of America ^aff003; Department of Pathology and Stony Brook Proteomics Center, Stony Brook University, Stony Brook, New York, United States of America ^aff004; Child Health Research Institute, Department of Pediatrics and of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America ^aff005; Division of Infectious Disease, Departments of Pediatrics and of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America ^aff006
Vyšlo v časopise: Novel replisome-associated proteins at cellular replication forks in EBV-transformed B lymphocytes. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008228
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008228

Souhrn

Epstein-Barr virus (EBV) is an oncogenic herpesvirus and WHO class 1 carcinogen that resides in B lymphocytes of nearly all humans. While silent in most, EBV can cause endemic Burkitt lymphoma in children and post-transplant lymphoproliferative disorders/lymphomas in immunocompromised hosts. The pathogenesis of such lymphomas is multifactorial but to a large extent depends on EBV’s ability to aggressively drive cellular DNA replication and B cell proliferation despite cell-intrinsic barriers to replication. One such barrier is oncogenic replication stress which hinders the progression of DNA replication forks. To understand how EBV successfully overcomes replication stress, we examined cellular replication forks in EBV-transformed B cells using iPOND (isolation of Proteins on Nascent DNA)-mass spectrometry and identified several cellular proteins that had not previously been linked to DNA replication. Of eight candidate replisome-associated proteins that we validated at forks in EBV-transformed cells and Burkitt lymphoma-derived cells, three zinc finger proteins (ZFPs) were upregulated early in B cells newly-infected with EBV in culture as well as expressed at high levels in EBV-infected B blasts in the blood of immunocompromised transplant recipients. Expressed highly in S- and G2-phase cells, knockdown of each ZFP resulted in stalling of proliferating cells in the S-phase, cleavage of caspase 3, and cell death. These proteins, newly-identified at replication forks of EBV-transformed and Burkitt lymphoma cells therefore contribute to cell survival and cell cycle progression, and represent novel targets for intervention of EBV-lymphomas while simultaneously offering a window into how the replication machinery may be similarly modified in other cancers.

Klíčová slova:

B cells – Cell cycle and cell division – DNA repair – DNA replication – Epstein-Barr virus – Flow cytometry – Synthesis phase – Viral replication

Zdroje

1. Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med. 2005;56:29–44. doi: 10.1146/annurev.med.56.082103.104727 15660500.

2. Allen UD, Preiksaitis JK, Practice ASTIDCo. Post-transplant Lymphoproliferative Disorders, EBV infection and Disease in Solid Organ Transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019:e13652. doi: 10.1111/ctr.13652 31230381.

3. Crombie JL, LaCasce AS. Epstein Barr Virus Associated B-Cell Lymphomas and Iatrogenic Lymphoproliferative Disorders. Front Oncol. 2019;9:109. doi: 10.3389/fonc.2019.00109 30899698; PubMed Central PMCID: PMC6416204.

4. Styczynski J, Einsele H, Gil L, Ljungman P. Outcome of treatment of Epstein-Barr virus-related post-transplant lymphoproliferative disorder in hematopoietic stem cell recipients: a comprehensive review of reported cases. Transpl Infect Dis. 2009;11(5):383–92. doi: 10.1111/j.1399-3062.2009.00411.x 19558376.

5. Al-Mansour Z, Nelson BP, Evens AM. Post-transplant lymphoproliferative disease (PTLD): risk factors, diagnosis, and current treatment strategies. Curr Hematol Malig Rep. 2013;8(3):173–83. doi: 10.1007/s11899-013-0162-5 23737188; PubMed Central PMCID: PMC4831913.

6. Orem J, Mbidde EK, Lambert B, de Sanjose S, Weiderpass E. Burkitt's lymphoma in Africa, a review of the epidemiology and etiology. Afr Health Sci. 2007;7(3):166–75. doi: 10.5555/afhs.2007.7.3.166 18052871; PubMed Central PMCID: PMC2269718.

7. Stanfield BA, Luftig MA. Recent advances in understanding Epstein-Barr virus. F1000Res. 2017;6:386. doi: 10.12688/f1000research.10591.1 28408983; PubMed Central PMCID: PMC5373418.

8. Koganti S, de la Paz A, Freeman AF, Bhaduri-McIntosh S. B lymphocytes from patients with a hypomorphic mutation in STAT3 resist Epstein-Barr virus-driven cell proliferation. J Virol. 2014;88(1):516–24. doi: 10.1128/JVI.02601-13 24173212; PubMed Central PMCID: PMC3911703.

9. Koganti S, Hui-Yuen J, McAllister S, Gardner B, Grasser F, Palendira U, et al. STAT3 interrupts ATR-Chk1 signaling to allow oncovirus-mediated cell proliferation. Proc Natl Acad Sci U S A. 2014;111(13):4946–51. doi: 10.1073/pnas.1400683111 24639502; PubMed Central PMCID: PMC3977268.

10. Smith J, Tho LM, Xu N, Gillespie DA. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res. 2010;108:73–112. Epub 2010/11/03. B978-0-12-380888-2.00003–0 [pii] doi: 10.1016/B978-0-12-380888-2.00003-0 21034966.

11. Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 2005;434(7035):864–70. Epub 2005/04/15. nature03482 [pii] doi: 10.1038/nature03482 15829956.

12. Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature. 2006;444(7119):633–7. Epub 2006/12/01. nature05268 [pii] doi: 10.1038/nature05268 17136093.

13. Halazonetis TD, Gorgoulis VG, Bartek J. An oncogene-induced DNA damage model for cancer development. Science. 2008;319(5868):1352–5. Epub 2008/03/08. 319/5868/1352 [pii] doi: 10.1126/science.1140735 18323444.

14. Hafez AY, Messinger JE, McFadden K, Fenyofalvi G, Shepard CN, Lenzi GM, et al. Limited nucleotide pools restrict Epstein-Barr virus-mediated B-cell immortalization. Oncogenesis. 2017;6(6):e349. Epub 2017/06/13. doi: 10.1038/oncsis.2017.46 28604764; PubMed Central PMCID: PMC5519195.

15. Mordasini V, Ueda S, Aslandogmus R, Berger C, Gysin C, Huhn D, et al. Activation of ATR-Chk1 pathway facilitates EBV-mediated transformation of primary tonsillar B-cells. Oncotarget. 2017;8(4):6461–74. Epub 2016/12/30. doi: 10.18632/oncotarget.14120 28031537; PubMed Central PMCID: PMC5351645.

16. Sirbu BM, McDonald WH, Dungrawala H, Badu-Nkansah A, Kavanaugh GM, Chen Y, et al. Identification of proteins at active, stalled, and collapsed replication forks using isolation of proteins on nascent DNA (iPOND) coupled with mass spectrometry. J Biol Chem. 2013;288(44):31458–67. doi: 10.1074/jbc.M113.511337 24047897; PubMed Central PMCID: PMC3814742.

17. Dungrawala H, Cortez D. Purification of proteins on newly synthesized DNA using iPOND. Methods Mol Biol. 2015;1228:123–31. doi: 10.1007/978-1-4939-1680-1_10 25311126; PubMed Central PMCID: PMC4384176.

18. Yarbro JW. Mechanism of action of hydroxyurea. Semin Oncol. 1992;19(3 Suppl 9):1–10. 1641648.

19. Charache S. Mechanism of action of hydroxyurea in the management of sickle cell anemia in adults. Semin Hematol. 1997;34(3 Suppl 3):15–21. 9317197.

20. Anantha RW, Vassin VM, Borowiec JA. Sequential and synergistic modification of human RPA stimulates chromosomal DNA repair. J Biol Chem. 2007;282(49):35910–23. doi: 10.1074/jbc.M704645200 17928296.

21. Sirbu BM, Couch FB, Feigerle JT, Bhaskara S, Hiebert SW, Cortez D. Analysis of protein dynamics at active, stalled, and collapsed replication forks. Genes Dev. 2011;25(12):1320–7. doi: 10.1101/gad.2053211 21685366; PubMed Central PMCID: PMC3127432.

22. Morio T, Kim H. Ku, Artemis, and ataxia-telangiectasia-mutated: signalling networks in DNA damage. Int J Biochem Cell Biol. 2008;40(4):598–603. doi: 10.1016/j.biocel.2007.12.007 18243767.

23. Li X, Burton EM, Bhaduri-McIntosh S. Chloroquine triggers Epstein-Barr virus replication through phosphorylation of KAP1/TRIM28 in Burkitt lymphoma cells. PLoS Pathog. 2017;13(3):e1006249. doi: 10.1371/journal.ppat.1006249 28249048.

24. White D, Rafalska-Metcalf IU, Ivanov AV, Corsinotti A, Peng H, Lee SC, et al. The ATM substrate KAP1 controls DNA repair in heterochromatin: regulation by HP1 proteins and serine 473/824 phosphorylation. Mol Cancer Res. 2012;10(3):401–14. doi: 10.1158/1541-7786.MCR-11-0134 22205726; PubMed Central PMCID: PMC4894472.

25. Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009;229(1):152–72. doi: 10.1111/j.1600-065X.2009.00782.x 19426221; PubMed Central PMCID: PMC3826168.

26. Wang LW, Shen H, Nobre L, Ersing I, Paulo JA, Trudeau S, et al. Epstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell Transformation. Cell Metab. 2019. doi: 10.1016/j.cmet.2019.06.003 31257153.

27. Lopez-Contreras AJ, Ruppen I, Nieto-Soler M, Murga M, Rodriguez-Acebes S, Remeseiro S, et al. A proteomic characterization of factors enriched at nascent DNA molecules. Cell Rep. 2013;3(4):1105–16. doi: 10.1016/j.celrep.2013.03.009 23545495; PubMed Central PMCID: PMC3714744.

28. Dembowski JA, DeLuca NA. Selective recruitment of nuclear factors to productively replicating herpes simplex virus genomes. PLoS Pathog. 2015;11(5):e1004939. doi: 10.1371/journal.ppat.1004939 26018390; PubMed Central PMCID: PMC4446364.

29. Kliszczak AE, Rainey MD, Harhen B, Boisvert FM, Santocanale C. DNA mediated chromatin pull-down for the study of chromatin replication. Sci Rep. 2011;1:95. doi: 10.1038/srep00095 22355613; PubMed Central PMCID: PMC3216581.

30. Ma J, Mi C, Wang KS, Lee JJ, Jin X. Zinc finger protein 91 (ZFP91) activates HIF-1alpha via NF-kappaB/p65 to promote proliferation and tumorigenesis of colon cancer. Oncotarget. 2016;7(24):36551–62. doi: 10.18632/oncotarget.9070 27144516; PubMed Central PMCID: PMC5095020.

31. Shahi P, Wang CY, Lawson DA, Slorach EM, Lu A, Yu Y, et al. ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression. Proc Natl Acad Sci U S A. 2017;114(12):3169–74. doi: 10.1073/pnas.1701690114 28258171; PubMed Central PMCID: PMC5373372.

32. Winczura K, Schmid M, Iasillo C, Molloy KR, Harder LM, Andersen JS, et al. Characterizing ZC3H18, a Multi-domain Protein at the Interface of RNA Production and Destruction Decisions. Cell Rep. 2018;22(1):44–58. Epub 2018/01/04. doi: 10.1016/j.celrep.2017.12.037 29298432; PubMed Central PMCID: PMC5770337.

33. Benz C, Mulindwa J, Ouna B, Clayton C. The Trypanosoma brucei zinc finger protein ZC3H18 is involved in differentiation. Mol Biochem Parasitol. 2011;177(2):148–51. doi: 10.1016/j.molbiopara.2011.02.007 21354218.

34. Kang MS, Kieff E. Epstein-Barr virus latent genes. Exp Mol Med. 2015;47:e131. doi: 10.1038/emm.2014.84 25613728; PubMed Central PMCID: PMC4314583.

35. Nikitin PA, Yan CM, Forte E, Bocedi A, Tourigny JP, White RE, et al. An ATM/Chk2-mediated DNA damage-responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells. Cell Host Microbe. 2010;8(6):510–22. Epub 2010/12/15. S1931-3128(10)00377-X [pii] doi: 10.1016/j.chom.2010.11.004 21147465; PubMed Central PMCID: PMC3049316.

36. Cimprich KA, Cortez D. ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol. 2008;9(8):616–27. Epub 2008/07/03. nrm2450 [pii] doi: 10.1038/nrm2450 18594563; PubMed Central PMCID: PMC2663384.

37. Paulsen RD, Cimprich KA. The ATR pathway: fine-tuning the fork. DNA Repair (Amst). 2007;6(7):953–66. Epub 2007/05/29. doi: 10.1016/j.dnarep.2007.02.015 17531546.

38. Saldivar JC, Cortez D, Cimprich KA. The essential kinase ATR: ensuring faithful duplication of a challenging genome. Nat Rev Mol Cell Biol. 2017;18(10):622–36. Epub 2017/08/16. doi: 10.1038/nrm.2017.67 28811666; PubMed Central PMCID: PMC5796526.

39. Zhou S, Yan Y, Chen X, Wang X, Zeng S, Qian L, et al. Roles of highly expressed PAICS in lung adenocarcinoma. Gene. 2019;692:1–8. doi: 10.1016/j.gene.2018.12.064 30641222.

40. Chakravarthi B, Rodriguez Pena MDC, Agarwal S, Chandrashekar DS, Hodigere Balasubramanya SA, Jabboure FJ, et al. A Role for De Novo Purine Metabolic Enzyme PAICS in Bladder Cancer Progression. Neoplasia. 2018;20(9):894–904. doi: 10.1016/j.neo.2018.07.006 30121007; PubMed Central PMCID: PMC6098199.

41. Chakravarthi B, Goswami MT, Pathi SS, Dodson M, Chandrashekar DS, Agarwal S, et al. Expression and role of PAICS, a de novo purine biosynthetic gene in prostate cancer. Prostate. 2018;78(9):693–4. doi: 10.1002/pros.23533 29744932.

42. Eissmann M, Schwamb B, Melzer IM, Moser J, Siele D, Kohl U, et al. A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes. PLoS One. 2013;8(5):e64873. doi: 10.1371/journal.pone.0064873 23717670; PubMed Central PMCID: PMC3661464.

43. Kwok WK, Ling MT, Yuen HF, Wong YC, Wang X. Role of p14ARF in TWIST-mediated senescence in prostate epithelial cells. Carcinogenesis. 2007;28(12):2467–75. doi: 10.1093/carcin/bgm185 17690110.

44. Zhang P, Branson OE, Freitas MA, Parthun MR. Identification of replication-dependent and replication-independent linker histone complexes: Tpr specifically promotes replication-dependent linker histone stability. BMC Biochem. 2016;17(1):18. doi: 10.1186/s12858-016-0074-9 27716023; PubMed Central PMCID: PMC5045598.

45. Th'ng JP, Sung R, Ye M, Hendzel MJ. H1 family histones in the nucleus. Control of binding and localization by the C-terminal domain. J Biol Chem. 2005;280(30):27809–14. doi: 10.1074/jbc.M501627200 15911621.

46. Liu X, Shao Z, Jiang W, Lee BJ, Zha S. PAXX promotes KU accumulation at DNA breaks and is essential for end-joining in XLF-deficient mice. Nat Commun. 2017;8:13816. doi: 10.1038/ncomms13816 28051062; PubMed Central PMCID: PMC5216128.

47. Verma S, De Jesus P, Chanda SK, Verma IM. SNW1, a Novel Transcriptional Regulator of the NF-kappaB Pathway. Mol Cell Biol. 2019;39(3). doi: 10.1128/MCB.00415-18 30397075; PubMed Central PMCID: PMC6336138.

48. Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ. Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. RNA. 2002;8(4):426–39. doi: 10.1017/s1355838202021088 11991638; PubMed Central PMCID: PMC1370266.

49. Zhang X, Yan C, Hang J, Finci LI, Lei J, Shi Y. An Atomic Structure of the Human Spliceosome. Cell. 2017;169(5):918–29 e14. Epub 2017/05/16. doi: 10.1016/j.cell.2017.04.033 28502770.

50. Bertram K, Agafonov DE, Liu WT, Dybkov O, Will CL, Hartmuth K, et al. Cryo-EM structure of a human spliceosome activated for step 2 of splicing. Nature. 2017;542(7641):318–23. Epub 2017/01/12. doi: 10.1038/nature21079 28076346.

51. Bres V, Yoshida T, Pickle L, Jones KA. SKIP interacts with c-Myc and Menin to promote HIV-1 Tat transactivation. Mol Cell. 2009;36(1):75–87. Epub 2009/10/13. doi: 10.1016/j.molcel.2009.08.015 19818711; PubMed Central PMCID: PMC2766281.

52. Zhou S, Fujimuro M, Hsieh JJ, Chen L, Hayward SD. A role for SKIP in EBNA2 activation of CBF1-repressed promoters. J Virol. 2000;74(4):1939–47. Epub 2000/01/22. doi: 10.1128/jvi.74.4.1939-1947.2000 10644367; PubMed Central PMCID: PMC111672.

53. Unoki M, Okutsu J, Nakamura Y. Identification of a novel human gene, ZFP91, involved in acute myelogenous leukemia. Int J Oncol. 2003;22(6):1217–23. 12738986.

54. Paschke L, Rucinski M, Ziolkowska A, Zemleduch T, Malendowicz W, Kwias Z, et al. ZFP91-a newly described gene potentially involved in prostate pathology. Pathol Oncol Res. 2014;20(2):453–9. doi: 10.1007/s12253-013-9716-z 24272675; PubMed Central PMCID: PMC3973948.

55. Jin X, Jin HR, Jung HS, Lee SJ, Lee JH, Lee JJ. An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-kappaB-inducing kinase via Lys63-linked ubiquitination. J Biol Chem. 2010;285(40):30539–47. doi: 10.1074/jbc.M110.129551 20682767; PubMed Central PMCID: PMC2945548.

56. Jin HR, Jin X, Lee JJ. Zinc-finger protein 91 plays a key role in LIGHT-induced activation of non-canonical NF-kappaB pathway. Biochem Biophys Res Commun. 2010;400(4):581–6. doi: 10.1016/j.bbrc.2010.08.107 20804734.

57. Peng Y, Shen X, Jiang H, Chen Z, Wu J, Zhu Y, et al. miR-188-5p Suppresses Gastric Cancer Cell Proliferation and Invasion via Targeting ZFP91. Oncol Res. 2018;27(1):65–71. doi: 10.3727/096504018X15191223015016 29471891.

58. Zheng Y, Yang C, Tong S, Ding Y, Deng W, Song D, et al. Genetic variation of long non-coding RNA TINCR contribute to the susceptibility and progression of colorectal cancer. Oncotarget. 2017;8(20):33536–43. doi: 10.18632/oncotarget.16538 28418933; PubMed Central PMCID: PMC5464888.

59. Blixt MKE, Konjusha D, Ring H, Hallbook F. Zinc finger gene nolz1 regulates the formation of retinal progenitor cells and suppresses the Lim3/Lhx3 phenotype of retinal bipolar cells in chicken retina. Dev Dyn. 2018;247(4):630–41. doi: 10.1002/dvdy.24607 29139167.

60. Urban N, Martin-Ibanez R, Herranz C, Esgleas M, Crespo E, Pardo M, et al. Nolz1 promotes striatal neurogenesis through the regulation of retinoic acid signaling. Neural Dev. 2010;5:21. doi: 10.1186/1749-8104-5-21 20735826; PubMed Central PMCID: PMC2939507.

61. Shahi P, Slorach EM, Wang CY, Chou J, Lu A, Ruderisch A, et al. The Transcriptional Repressor ZNF503/Zeppo2 Promotes Mammary Epithelial Cell Proliferation and Enhances Cell Invasion. J Biol Chem. 2015;290(6):3803–13. doi: 10.1074/jbc.M114.611202 25538248; PubMed Central PMCID: PMC4319044.

62. Lu G, Zhang Y. MicroRNA-340-5p suppresses non-small cell lung cancer cell growth and metastasis by targeting ZNF503. Cell Mol Biol Lett. 2019;24:34. doi: 10.1186/s11658-019-0161-1 31160893; PubMed Central PMCID: PMC6537386.

63. Calabretta S, Richard S. Emerging Roles of Disordered Sequences in RNA-Binding Proteins. Trends Biochem Sci. 2015;40(11):662–72. doi: 10.1016/j.tibs.2015.08.012 26481498.

64. Jarvelin AI, Noerenberg M, Davis I, Castello A. The new (dis)order in RNA regulation. Cell Commun Signal. 2016;14:9. doi: 10.1186/s12964-016-0132-3 27048167; PubMed Central PMCID: PMC4822317.

65. Luo J, Emanuele MJ, Li D, Creighton CJ, Schlabach MR, Westbrook TF, et al. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell. 2009;137(5):835–48. Epub 2009/06/06. doi: 10.1016/j.cell.2009.05.006 19490893; PubMed Central PMCID: PMC2768667.

66. Gewurz BE, Towfic F, Mar JC, Shinners NP, Takasaki K, Zhao B, et al. Genome-wide siRNA screen for mediators of NF-kappaB activation. Proc Natl Acad Sci U S A. 2012;109(7):2467–72. doi: 10.1073/pnas.1120542109 22308454; PubMed Central PMCID: PMC3289371.

67. Ribeyre C, Zellweger R, Chauvin M, Bec N, Larroque C, Lopes M, et al. Nascent DNA Proteomics Reveals a Chromatin Remodeler Required for Topoisomerase I Loading at Replication Forks. Cell Rep. 2016;15(2):300–9. doi: 10.1016/j.celrep.2016.03.027 27050524.

68. Dabral P, Uppal T, Rossetto CC, Verma SC. Minichromosome Maintenance Proteins Cooperate with LANA during the G1/S Phase of the Cell Cycle To Support Viral DNA Replication. J Virol. 2019;93(7). Epub 2019/01/18. doi: 10.1128/JVI.02256-18 30651368; PubMed Central PMCID: PMC6430539.

69. Macheret M, Halazonetis TD. DNA replication stress as a hallmark of cancer. Annu Rev Pathol. 2015;10:425–48. Epub 2015/01/27. doi: 10.1146/annurev-pathol-012414-040424 25621662.

70. Hui-Yuen J, Koganti S, Bhaduri-McIntosh S. Human B cell immortalization for monoclonal antibody production. Methods Mol Biol. 2014;1131:183–9. doi: 10.1007/978-1-62703-992-5_11 24515466.

71. Li X, Burton EM, Koganti S, Zhi J, Doyle F, Tenenbaum SA, et al. KRAB-ZFP Repressors Enforce Quiescence of Oncogenic Human Herpesviruses. J Virol. 2018;92(14). doi: 10.1128/JVI.00298-18 29695433; PubMed Central PMCID: PMC6026741.