Palabras clave
Células NK
Células T CD8+
Inmunodeficiencias primarias
Vacunas
Resumen
El virus Epstein-Barr es un virus gamma herpes que afecta exclusivamente a humanos; fue el primer virus oncogénico descrito y se ha relacionado con más de siete diferentes tipos de cáncer. Curiosamente, el intercambio de genes debido a infecciones virales ha permitido la evolución de los organismos celulares, favoreciendo el desarrollo de nuevas funciones y supervivencia del hospedero. El virus Epstein-Barr comparte cientos de millones de años de coevolución con la especie humana y más del 95% de la población adulta mundial se ha infectado en algún momento de su vida. La infección se adquiere principalmente durante la infancia, y en la mayoría de los casos aparece sin ninguna manifestación grave aparente. Sin embargo, en los adolescentes y la población joven-adulta, alrededor de un 10 a 30% evolucionan a mononucleosis infecciosa. Las células NK y T CD8+ son células citotóxicas cruciales durante las respuestas antivirales y se ha demostrado que controlan y eliminan la infección por el virus Epstein-Barr. No obstante, cuando se afecta su función efectora, el desenlace puede ser fatal. El objetivo de esta revisión es describir la infección por el virus Epstein-Barr y el papel decisivo de las células NK y T CD8+ durante el control y eliminación de la infección. Además, se discuten brevemente los principales defectos genéticos que afectan a estas células y conllevan a la incapacidad para eliminar el virus. Finalmente, se resalta la necesidad de elaborar una vacuna efectiva contra el virus Epstein-Barr y cómo podrían evitarse los procesos neoplásicos y enfermedades autoinmunes.
Referencias
Magrath I. Denis Burkitt and the African lymphoma. Ecancermedicalscience. 2009;3(1). doi:10.3332/ECANCER.2009.159
Burkitt D. A sarcoma involving the jaws in african children. Br J Surg. 1958;46(197):218-223. doi:10.1002/BJS.18004619704
Epstein A. Why and how epstein-barr virus was discovered 50 years ago. Epstein Barr Virus. 2015;1:3-15. doi:10.1007/978-3-319-22822-8_1/COVER
Epstein MA, Achong BG, Barr YM. VIRUS PARTICLES IN CULTURED LYMPHOBLASTS FROM BURKITT’S LYMPHOMA. Lancet (London, England). 1964;1(7335):702-703. doi:10.1016/S0140-6736(64)91524-7
Shope T, Dechairo D, Miller G. Malignant Lymphoma in Cottontop Marmosets after Inoculation with Epstein-Barr Virus. Proc Natl Acad Sci. 1973;70(9):2487-2491. doi:10.1073/PNAS.70.9.2487
Young LS, Yap LF, Murray PG. Epstein–Barr virus: more than 50 years old and still providing surprises. Nat Rev Cancer 2016 1612. 2016;16(12):789-802. doi:10.1038/nrc.2016.92
Latour S, Fischer A. Signaling pathways involved in the T-cell-mediated immunity against Epstein-Barr virus: Lessons from genetic diseases. Immunol Rev. 2019;291(1):174-189. doi:10.1111/imr.12791
Spear PG, Longnecker R. Herpesvirus Entry: an Update. J Virol. 2003;77(19):10179-10185. doi:10.1128/JVI.77.19.10179-10185.2003/ASSET/E0C41003-6048-4027-B047-DDD182837D2F/ASSETS/GRAPHIC/JV1930587002.JPEG
Tangye SG. Genetic susceptibility to EBV infection: insights from inborn errors of immunity. Hum Genet. 2020;139(6-7):885-901. doi:10.1007/s00439-020-02145-3
Münz C. Cytotoxicity in Epstein Barr virus specific immune control. Curr Opin Virol. 2021;46:1-8. doi:10.1016/j.coviro.2020.07.011
Khan G, Hashim MJ. Global burden of deaths from Epstein-Barr virus attributable malignancies 1990-2010. Infect Agent Cancer. 2014;9(1). doi:10.1186/1750-9378-9-38
Chijioke O, Landtwing V, Münz C. NK cell influence on the outcome of primary Epstein-Barr virus infection. Front Immunol. 2016;7(AUG):1-7. doi:10.3389/fimmu.2016.00323
Münz C. Natural killer cell responses to human oncogenic γ-herpesvirus infections. Semin Immunol. 2022;60(September):101652. doi:10.1016/j.smim.2022.101652
Cruz-Muñoz ME, Fuentes-Pananá EM. Beta and gamma human herpesviruses: Agonistic and antagonistic interactions with the host immune system. Front Microbiol. 2018;8(JAN). doi:10.3389/fmicb.2017.02521
Münz C. Epstein Barr virus — a tumor virus that needs cytotoxic lymphocytes to persist asymptomatically. Curr Opin Virol. 2016;20:34-39. doi:10.1016/j.coviro.2016.08.010
Calvani M, Alessandri C, Paolone G, Rosengard L, Di Caro A, De Franco D. Correlation between Epstein Barr virus antibodies, serum IgE and atopic disease. Pediatr Allergy Immunol. 1997;8(2):91-96. doi:10.1111/J.1399-3038.1997.TB00150.X
Nilsson C, Larsson Sigfrinius AK, Montgomery SM, et al. Epstein-Barr virus and cytomegalovirus are differentially associated with numbers of cytokine-producing cells and early atopy. Clin Exp Allergy. 2009;39(4):509-517. doi:10.1111/J.1365-2222.2008.03147.X
Barton ES, White DW, Cathelyn JS, et al. Herpesvirus latency confers symbiotic protection from bacterial infection. Nat 2007 4477142. 2007;447(7142):326-329. doi:10.1038/nature05762
Cohen JI, Fauci AS, Varmus H, Nabel GJ. Epstein-Barr virus: An important vaccine target for cancer prevention. Sci Transl Med. 2011;3(107):3-6. doi:10.1126/scitranslmed.3002878
Tangye SG, Palendira U, Edwards ESJ. Human immunity against EBV-lessons from the clinic. J Exp Med. 2017;214(2):269-283. doi:10.1084/jem.20161846
Jiang R, Gu X, Nathan CA, Hutt-Fletcher L. Laser-capture microdissection of oropharyngeal epithelium indicates restriction of Epstein-Barr virus receptor/CD21 mRNA to tonsil epithelial cells. J Oral Pathol Med. 2008;37(10):626-633. doi:10.1111/J.1600-0714.2008.00681.X
Ressing ME, Gram AM, Gram AM, Hooykaas MJG, Piersma SJ, Wiertz EJHJ. Immune Evasion by Epstein-Barr Virus. Curr Top Microbiol Immunol. 2015;391:355-381. doi:10.1007/978-3-319-22834-1_12
Münz C. Immune Escape by Non-coding RNAs of the Epstein Barr Virus. Front Microbiol. 2021;12(June):1-9. doi:10.3389/fmicb.2021.657387
Houldcroft CJ, Kellam P. Host genetics of Epstein-Barr virus infection, latency and disease. Rev Med Virol. 2015;25(2):71-84. doi:10.1002/rmv.1816
Hochberg D, Middeldorp JM, Catalina M, Sullivan JL, Luzuriaga K, Thorley-Lawson DA. Demonstration of the Burkitt’s lymphoma Epstein-Barr virus phenotype in dividing latently infected memory cells in vivo. Proc Natl Acad Sci U S A. 2004;101(1):239-244. doi:10.1073/PNAS.2237267100
Laichalk LL, Thorley-Lawson DA. Terminal Differentiation into Plasma Cells Initiates the Replicative Cycle of Epstein-Barr Virus In Vivo. J Virol. 2005;79(2):1296-1307. doi:10.1128/JVI.79.2.1296-1307.2005/ASSET/8631D52B-4C32-4ABE-B675-093AB3595AA4/ASSETS/GRAPHIC/ZJV0020556890008.JPEG
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. 2008;9(5):503-510. doi:10.1038/ni1582
Prager I, Watzl C. Mechanisms of natural killer cell-mediated cellular cytotoxicity. J Leukoc Biol. 2019;105(6):1319-1329. doi:10.1002/JLB.MR0718-269R
Della Chiesa M, De Maria A, Muccio L, Bozzano F, Sivori S, Moretta L. Human NK Cells and Herpesviruses: Mechanisms of Recognition, Response and Adaptation. Front Microbiol. 2019;10(October):1-9. doi:10.3389/fmicb.2019.02297
Zhang N, Bevan MJ. CD8+ T Cells: Foot Soldiers of the Immune System. Immunity. 2011;35(2):161-168. doi:10.1016/j.immuni.2011.07.010
Cohen JI. Primary Immunodeficiencies Associated with EBV Disease. Curr Top Microbiol Immunol. 2015;390(Pt 1):241-265. doi:10.1007/978-3-319-22822-8_10
Rickinson AB, Long HM, Palendira U, Münz C, Hislop AD. Cellular immune controls over Epstein-Barr virus infection: New lessons from the clinic and the laboratory. Trends Immunol. 2014;35(4):159-169. doi:10.1016/j.it.2014.01.003
Tangye SG, Latour S. Primary immunodeficiencies reveal the molecular requirements for effective host defense against EBV infection. Blood. 2020;135(9):644-655. doi:10.1182/BLOOD.2019000928
Shaw RK, Issekutz AC, Fraser R, et al. Bilateral adrenal EBV-associated smooth muscle tumors in a child with a natural killer cell deficiency. Published online 2012. doi:10.1182/blood-2011-10-385377
Strowig T, Brilot F, Arrey F, et al. Tonsilar NK Cells Restrict B Cell Transformation by the Epstein-Barr Virus via IFN-γ. PLOS Pathog. 2008;4(2):e27. doi:10.1371/JOURNAL.PPAT.0040027
Lanier LL. NKG2D receptor and its ligands in host defense. Cancer Immunol Res. 2015;3(6):575-582. doi:10.1158/2326-6066.CIR-15-0098
Antsiferova O, Müller A, Rämer PC, et al. Adoptive transfer of EBV specific CD8+ T cell clones can transiently control EBV infection in humanized mice. PLoS Pathog. 2014;10(8). doi:10.1371/JOURNAL.PPAT.1004333
Tangye SG, Al-Herz W, Bousfiha A, et al. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. Springer US; 2022. doi:10.1007/s10875-022-01289-3
Kuehn HS, Niemela JE, Rangel-Santos A, et al. Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans. Blood. 2013;121(16):3117-3125. doi:10.1182/BLOOD-2012-12-469544
Lee JH, Choi J, Ahn YO, Kim TM, Heo DS. CD21-independent Epstein-Barr virus entry into NK cells. Cell Immunol. 2018;327(January):21-25. doi:10.1016/j.cellimm.2018.01.011
Rohr J, Beutel K, Maul-Pavicic A, et al. Atypical familial hemophagocytic lymphohistiocytosis due to mutations in UNC13D and STXBP2 overlaps with primary immunodeficiency diseases. Haematologica. 2010;95(12):2080-2087. doi:10.3324/HAEMATOL.2010.029389
Katano H, Ali MA, Patera AC, et al. Chronic active Epstein-Barr virus infection associated with mutations in perforin that impair its maturation. Blood. 2004;103(4):1244-1252. doi:10.1182/BLOOD-2003-06-2171
Sheng L, Zhang W, Gu J, Shen K, Luo H, Yang Y. Novel mutations of STXBP2 and LYST associated with adult haemophagocytic lymphohistiocytosis with Epstein-Barr virus infection: a case report. BMC Med Genet. 2019;20(1). doi:10.1186/S12881-019-0765-3
Linka RM, Risse SL, Bienemann K, et al. Loss-of-function mutations within the IL-2 inducible kinase ITK in patients with EBV-associated lymphoproliferative diseases. Leukemia. 2012;26(5):963-971. doi:10.1038/LEU.2011.371
Winter S, Martin E, Boutboul D, et al. Loss of RASGRP1 in humans impairs T-cell expansion leading to Epstein-Barr virus susceptibility. EMBO Mol Med. 2018;10(2):188-199. doi:10.15252/EMMM.201708292
Hoshino A, Takashima T, Yoshida K, et al. Dysregulation of Epstein-Barr Virus Infection in Hypomorphic ZAP70 Mutation. J Infect Dis. 2018;218(5):825-834. doi:10.1093/INFDIS/JIY231
Salzer E, Daschkey S, Choo S, et al. Combined immunodeficiency with life-threatening EBV-associated lymphoproliferative disorder in patients lacking functional CD27. Haematologica. 2013;98(3):473-478. doi:10.3324/HAEMATOL.2012.068791
Abolhassani H, Edwards ESJ, Ikinciogullari A, et al. Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency. J Exp Med. 2017;214(1):91-106. doi:10.1084/JEM.20160849
Alosaimi MF, Hoenig M, Jaber F, et al. Immunodeficiency and EBV-induced lymphoproliferation caused by 4-1BB deficiency. J Allergy Clin Immunol. 2019;144(2):574-583.e5. doi:10.1016/J.JACI.2019.03.002
Li FY, Chaigne-Delalande B, Su H, Uzel G, Matthews H, Lenardo MJ. XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. Blood. 2014;123(14):2148-2152. doi:10.1182/BLOOD-2013-11-538686
Latour S, Aguilar C. XIAP deficiency syndrome in humans. Semin Cell Dev Biol. 2015;39:115-123. doi:10.1016/J.SEMCDB.2015.01.015
Cohen JI, Dropulic L, Hsu AP, et al. Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers. Clin Infect Dis. 2016;63(1):41-47. doi:10.1093/CID/CIW160
Gineau L, Cognet C, Kara N, et al. Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency. J Clin Invest. 2012;122(3):821-832. doi:10.1172/JCI61014
Martin E, Palmic N, Sanquer S, et al. CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation. Nature. 2014;510(7504):288-292. doi:10.1038/NATURE13386
Nagy N, Klein E. Deficiency of the proapoptotic SAP function in X-linked lymphoproliferative disease aggravates Epstein-Barr virus (EBV) induced mononucleosis and promotes lymphoma development. Immunol Lett. 2010;130(1-2):13-18. doi:10.1016/J.IMLET.2010.01.002
Palendira U, Low C, Chan A, et al. Molecular Pathogenesis of EBV Susceptibility in XLP as Revealed by Analysis of Female Carriers with Heterozygous Expression of SAP. PLOS Biol. 2011;9(11):e1001187. doi:10.1371/JOURNAL.PBIO.1001187
Panchal N, Booth C, Cannons JL, Schwartzberg PL. X-linked lymphoproliferative disease type 1: A clinical and molecular perspective. Front Immunol. 2018;9(APR):666. doi:10.3389/FIMMU.2018.00666/BIBTEX
Weiner GJ. Rituximab: Mechanism of Action. Semin Hematol. 2010;47(2):115-123. doi:10.1053/J.SEMINHEMATOL.2010.01.011
Mark BJ, Knutsen AP. Rituximab Treatment to Control Epstein-Barr Virus (EBV) Infection in X-Linked Lymphoproliferative Disorder (XLP). J Allergy Clin Immunol. 2006;117(2):S106. doi:10.1016/j.jaci.2005.12.424
Houen G, Trier NH. Epstein-Barr Virus and Systemic Autoimmune Diseases. Front Immunol. 2021;11(January):1-13. doi:10.3389/fimmu.2020.587380
Trier NH, Holm BE, Heiden J, et al. Antibodies to a strain-specific citrullinated Epstein-Barr virus peptide diagnoses rheumatoid arthritis. Sci Reports 2018 81. 2018;8(1):1-11. doi:10.1038/s41598-018-22058-6
Trier N, Izarzugaza J, Chailyan A, Marcatili P, Houen G. Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis. Int J Mol Sci 2018, Vol 19, Page 317. 2018;19(1):317. doi:10.3390/IJMS19010317
Masuoka S, Kusunoki N, Takamatsu R, et al. Epstein-Barr virus infection and variants of Epstein-Barr nuclear antigen-1 in synovial tissues of rheumatoid arthritis. PLoS One. 2018;13(12). doi:10.1371/JOURNAL.PONE.0208957
Croia C, Serafini B, Bombardieri M, et al. Epstein-Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis. Ann Rheum Dis. 2013;72(9):1559-1568. doi:10.1136/ANNRHEUMDIS-2012-202352
Harley J, joint JJ-B of the N hospital for, 2006 undefined. Epstein-Barr virus infection induces lupus autoimmunity. search.ebscohost.com. Accessed April 23, 2023. https://search.ebscohost.com/login.aspx?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=19369719&AN=22973199&h=tV5OZeUiUTy7XgrpUdnOYH93VEtemZQ73NvtTuGDVwAZXFF5D4cDncJA7Di3cpWTxjqbz7COXulpV4lA8Ph5aw%3D%3D&crl=c
Läderach F, Münz C. Epstein Barr Virus Exploits Genetic Susceptibility to Increase Multiple Sclerosis Risk. Microorg 2021, Vol 9, Page 2191. 2021;9(11):2191. doi:10.3390/MICROORGANISMS9112191
Bjornevik K, Cortese M, Healy BC, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science (80- ). 2022;375(6578):296-301. doi:10.1126/SCIENCE.ABJ8222
Wang Z, Kennedy PG, Dupree C, et al. Antibodies from Multiple Sclerosis Brain Identified Epstein-Barr Virus Nuclear Antigen 1 & 2 Epitopes which Are Recognized by Oligoclonal Bands. J Neuroimmune Pharmacol. 2021;16(3):567-580. doi:10.1007/S11481-020-09948-1/FIGURES/6
Van Nierop GP, Mautner J, Mitterreiter JG, Hintzen RQ, Verjans GMGM. Intrathecal CD8 T-cells of multiple sclerosis patients recognize lytic Epstein-Barr virus proteins. Mult Scler. 2016;22(3):279-291. doi:10.1177/1352458515588581
Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017;376(3):221-234. doi:10.1056/NEJMOA1601277
Barzilai O, Sherer Y, Ram M, Izhaky D, Anaya JM, Shoenfeld Y. Epstein-Barr virus and cytomegalovirus in autoimmune diseases: Are they truly notorious? A preliminary report. Ann N Y Acad Sci. 2007;1108:567-577. doi:10.1196/ANNALS.1422.059
Temajo NO, Howard N. The mosaic of environment involvement in autoimmunity: The abrogation of viral latency by stress, a non-infectious environmental agent, is an intrinsic prerequisite prelude before viruses can rank as infectious environmental agents that trigger autoimmune diseases. Autoimmun Rev. 2014;13(6):635-640. doi:10.1016/J.AUTREV.2013.12.003
Zhong L, Krummenacher C, Zhang W, et al. Urgency and necessity of Epstein-Barr virus prophylactic vaccines. npj Vaccines 2022 71. 2022;7(1):1-14. doi:10.1038/s41541-022-00587-6
Cui X, Snapper CM. Epstein Barr Virus: Development of Vaccines and Immune Cell Therapy for EBV-Associated Diseases. Front Immunol. 2021;12:4081. doi:10.3389/FIMMU.2021.734471/BIBTEX
Cohen JI. Vaccine development for Epstein-Barr virus. Adv Exp Med Biol. 2018;1045:477-493. doi:10.1007/978-981-10-7230-7_22/COVER
Münz C. Epstein-Barr virus-specific immune control by innate lymphocytes. Front Immunol. 2017;8(NOV):1-7. doi:10.3389/fimmu.2017.01658
Vély F, Barlogis V, Vallentin B, et al. Evidence of innate lymphoid cell redundancy in humans. Nat Immunol. 2016;17(11):1291-1299. doi:10.1038/ni.3553
Djaoud Z, Guethlein LA, Horowitz A, et al. Two alternate strategies for innate immunity to Epstein-Barr virus: One using NK cells and the other NK cells and γδ T cells. J Exp Med. 2017;214(6):1827-1841. doi:10.1084/JEM.20161017
Biron CA, Byron KS, Sullivan JL. Severe Herpesvirus Infections in an Adolescent without Natural Killer Cells. http://dx.doi.org/101056/NEJM198906293202605. 1989;320(26):1731-1735. doi:10.1056/NEJM198906293202605
Orange JS. Natural killer cell deficiency. J Allergy Clin Immunol. 2013;132(3):515-525. doi:10.1016/j.jaci.2013.07.020
Orange JS, Mace EM, French AR, Yokoyama WM, Fehniger TA, Cooper MA. Comment on: Evidence of innate lymphoid cell redundancy in humans. Nat Immunol. 2018;19(8):788-789. doi:10.1038/s41590-018-0164-5
Mace EM, Orange JS. Genetic causes of human NK cell deficiency and their effect on NK cell subsets. Front Immunol. 2016;7(DEC):545. doi:10.3389/FIMMU.2016.00545/BIBTEX
Mace EM, Paust S, Conte MI, et al. Human NK cell deficiency as a result of biallelic mutations in MCM10. J Clin Invest. 2020;130(10):5272-5286. doi:10.1172/JCI134966
Grant ML, Bollard CM. Cell therapies for hematological malignancies: don’t forget non-gene-modified t cells! Published online 2017. doi:10.1016/j.blre.2017.11.004
Icheva V, Kayser S, Wolff D, et al. Adoptive transfer of Epstein-Barr virus (EBV) nuclear antigen 1-specific T cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation. J Clin Oncol. 2013;31(1):39-48. doi:10.1200/JCO.2011.39.8495
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