{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:10:25Z","timestamp":1789161025565,"version":"build-2803163510"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Midwestern University Intramural Funds"},{"name":"Midwestern University Core Facility"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epstein\u2013Barr Virus (EBV) exists in a latent state in 90% of the world\u2019s population and is linked to numerous cancers, such as Burkitt\u2019s Lymphoma, Hodgkin\u2019s, and non-Hodgkin\u2019s Lymphoma. One EBV latency protein, latency membrane protein 2A (LMP2A), is expressed in multiple latency phenotypes. LMP2A signaling has been extensively studied and one target of LMP2A is the mammalian target of rapamycin (mTOR). Since mTOR has been linked to reprogramming tumor metabolism and increasing levels of hypoxia-inducible factor 1 \u03b1 (HIF-1\u03b1), we hypothesized that LMP2A would increase HIF-1\u03b1 levels to enhance ATP generation in B lymphoma cell lines. Our data indicate that LMP2A increases ATP generation in multiple Burkitt lymphoma cell lines that were dependent on HIF-1\u03b1. Subsequent studies indicate that the addition of the mTOR inhibitor, rapamycin, blocked the LMP2A-dependent increase in HIF-1\u03b1. Further studies demonstrate that LMP2A does not increase HIF-1\u03b1 levels by increasing HIF-1\u03b1 RNA or STAT3 activation. In contrast, LMP2A and mTOR-dependent increase in HIF-1\u03b1 required mTOR-dependent phosphorylation of p70 S6 Kinase and 4E-BP1. These findings implicate the importance of LMP2A in promoting B cell lymphoma survival by increasing ATP generation and identifying potential pharmaceutical targets to treat EBV-associated tumors.<\/jats:p>","DOI":"10.3390\/ijms25073944","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T01:26:10Z","timestamp":1712021170000},"page":"3944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Epstein\u2013Barr Virus Latent Membrane Protein 2A (LMP2A) Enhances ATP Production in B Cell Tumors through mTOR and HIF-1\u03b1"],"prefix":"10.3390","volume":"25","author":[{"given":"Ryan","family":"Incrocci","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalinda","family":"Monroy Del Toro","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Devitt","sequence":"additional","affiliation":[{"name":"Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody","family":"Salimian","sequence":"additional","affiliation":[{"name":"Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamaljit","family":"Braich","sequence":"additional","affiliation":[{"name":"Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-6933","authenticated-orcid":false,"given":"Michelle","family":"Swanson-Mungerson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA"},{"name":"Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"key":"ref_1","unstructured":"Knipe, D.M., and Howley, P.M. (2013). Fields Virology, Wolters Kluwer\/Lippincott Williams & Wilkins Health. [6th ed.]. 2 volumes."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/mp.53.5.262","article-title":"Hodgkin\u2019s disease and the Epstein-Barr virus","volume":"53","author":"Flavell","year":"2000","journal-title":"Mol. Pathol."},{"key":"ref_3","first-page":"14656","article-title":"Epstein-Barr Virus-associated lymphoproliferative disorders: Experimental and clinical developments","volume":"8","author":"Geng","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.coviro.2015.09.007","article-title":"Epstein-Barr virus latency: Current and future perspectives","volume":"14","author":"Kempkes","year":"2015","journal-title":"Curr. Opin. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1172\/JCI61245","article-title":"Hodgkin lymphoma","volume":"122","author":"Kuppers","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nrmicro2015","article-title":"The curious case of the tumour virus: 50 years of Burkitt\u2019s lymphoma","volume":"6","author":"Allday","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1056\/NEJMra032015","article-title":"Persistence of the Epstein-Barr virus and the origins of associated lymphomas","volume":"350","author":"Gross","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s12985-023-02187-9","article-title":"Epstein-Barr virus infection: The micro and macro worlds","volume":"20","author":"Huang","year":"2023","journal-title":"Virol. J."},{"key":"ref_9","first-page":"151","article-title":"Latent Membrane Protein 2 (LMP2)","volume":"391","author":"Cen","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"222","DOI":"10.2478\/s11658-008-0045-2","article-title":"The signaling pathways of Epstein-Barr virus-encoded latent membrane protein 2A (LMP2A) in latency and cancer","volume":"14","author":"Pang","year":"2009","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"26318","DOI":"10.1073\/pnas.2007946117","article-title":"Rewiring of B cell receptor signaling by Epstein-Barr virus LMP2A","volume":"117","author":"Fish","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9115","DOI":"10.1128\/JVI.74.19.9115-9124.2000","article-title":"The LMP2A ITAM is essential for providing B cells with development and survival signals in vivo","volume":"74","author":"Merchant","year":"2000","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wasil, L.R., Tomaszewski, M.J., Hoji, A., and Rowe, D.T. (2013). The effect of Epstein-Barr virus Latent Membrane Protein 2 expression on the kinetics of early B cell infection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054010"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/blood-2013-07-517649","article-title":"Epstein-Barr virus latent membrane protein 2A enhances MYC-driven cell cycle progression in a mouse model of B lymphoma","volume":"123","author":"Fish","year":"2014","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8619","DOI":"10.1038\/sj.onc.1207905","article-title":"Epstein-Barr virus (EBV) LMP2A mediates B-lymphocyte survival through constitutive activation of the Ras\/PI3K\/Akt pathway","volume":"23","author":"Portis","year":"2004","journal-title":"Oncogene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1006\/viro.1999.9964","article-title":"Tyrosines 60, 64, and 101 of Epstein-Barr virus LMP2A are not essential for blocking B cell signal transduction","volume":"263","author":"Swart","year":"1999","journal-title":"Virology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5499","DOI":"10.1128\/JVI.79.9.5499-5506.2005","article-title":"Modulation of the cell growth regulator mTOR by Epstein-Barr virus-encoded LMP2A","volume":"79","author":"Moody","year":"2005","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-230X(02)86001-8","article-title":"Coordinate regulation of translation by the PI 3-kinase and mTOR pathways","volume":"86","author":"Martin","year":"2002","journal-title":"Adv. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1158\/2159-8290.CD-11-0218","article-title":"PI3K and STAT3: A new alliance","volume":"1","author":"Vogt","year":"2011","journal-title":"Cancer Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.virol.2016.10.015","article-title":"Epstein-Barr Virus Latent Membrane Protein 2A (LMP2A) enhances IL-10 production through the activation of Bruton\u2019s tyrosine kinase and STAT3","volume":"500","author":"Incrocci","year":"2017","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"556","DOI":"10.3389\/fonc.2018.00556","article-title":"Metabolic Reprogramming of Non-Hodgkin\u2019s B-Cell Lymphomas and Potential Therapeutic Strategies","volume":"8","author":"Ricci","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.molcel.2010.06.022","article-title":"Activation of a metabolic gene regulatory network downstream of mTOR complex 1","volume":"39","author":"Duvel","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1158\/2159-8290.CD-12-0345","article-title":"Cancer cell metabolism: One hallmark, many faces","volume":"2","author":"Cantor","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2174\/1568009611313030003","article-title":"Oxygen-independent regulation of HIF-1: Novel involvement of PI3K\/AKT\/mTOR pathway in cancer","volume":"13","author":"Agani","year":"2013","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1038\/onc.2014.164","article-title":"mTORC1 drives HIF-1alpha and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3","volume":"34","author":"Dodd","year":"2015","journal-title":"Oncogene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.1182\/blood-2005-12-4788","article-title":"Antigen receptor-mediated changes in glucose metabolism in B lymphocytes: Role of phosphatidylinositol 3-kinase signaling in the glycolytic control of growth","volume":"107","author":"Doughty","year":"2006","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.trecan.2017.12.006","article-title":"B-Cell Metabolic Remodeling and Cancer","volume":"4","author":"Franchina","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Albanese, A., Daly, L.A., Mennerich, D., Kietzmann, T., and See, V. (2020). The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating Its Localisation, Stability, and Activity. Int. J. Mol. Sci., 22.","DOI":"10.20944\/preprints202012.0112.v1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41467-017-02683-x","article-title":"Hypoxia-inducible factor-1alpha is a critical transcription factor for IL-10-producing B cells in autoimmune disease","volume":"9","author":"Meng","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13045-022-01292-6","article-title":"Hypoxia-inducible factors: Master regulators of hypoxic tumor immune escape","volume":"15","author":"Wu","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13045-019-0754-1","article-title":"Targeting mTOR for cancer therapy","volume":"12","author":"Hua","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1126\/science.1228792","article-title":"Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1","volume":"339","author":"Howell","year":"2013","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11988","DOI":"10.1073\/pnas.1310230110","article-title":"Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers","volume":"110","author":"Pourdehnad","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Shannon-Lowe, C., Rickinson, A.B., and Bell, A.I. (2017). Epstein-Barr virus-associated lymphomas. Philos. Trans. R. Soc. Lond. B Biol. Sci., 372.","DOI":"10.1098\/rstb.2016.0271"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yang, T., You, C., Meng, S., Lai, Z., Ai, W., and Zhang, J. (2022). EBV Infection and Its Regulated Metabolic Reprogramming in Nasopharyngeal Tumorigenesis. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.935205"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S0140-6736(64)91524-7","article-title":"Virus Particles in Cultured Lymphoblasts from Burkitt\u2019s Lymphoma","volume":"1","author":"Epstein","year":"1964","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.2147\/OTT.S158206","article-title":"The role of HIF-1alpha in chemo-\/radioresistant tumors","volume":"11","author":"Xia","year":"2018","journal-title":"Onco Targets Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.immuni.2013.04.005","article-title":"Metabolic pathways in immune cell activation and quiescence","volume":"38","author":"Pearce","year":"2013","journal-title":"Immunity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.virol.2015.02.038","article-title":"Viral activation of cellular metabolism","volume":"479\u2013480","author":"Sanchez","year":"2015","journal-title":"Virology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Gaballah, A., and Bartosch, B. (2022). An Update on the Metabolic Landscape of Oncogenic Viruses. Cancers, 14.","DOI":"10.3390\/cancers14235742"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.virol.2014.02.027","article-title":"Hypoxia-inducible factor 1 and its role in viral carcinogenesis","volume":"456","author":"Cuninghame","year":"2014","journal-title":"Virology"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Piccaluga, P.P., Weber, A., Ambrosio, M.R., Ahmed, Y., and Leoncini, L. (2018). Epstein-Barr Virus-Induced Metabolic Rearrangements in Human B-Cell Lymphomas. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01233"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41392-020-00376-4","article-title":"Targeting the signaling in Epstein-Barr virus-associated diseases: Mechanism, regulation, and clinical study","volume":"6","author":"Cao","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e00238-19","DOI":"10.1128\/JVI.00238-19","article-title":"Mechanisms of B-Cell Oncogenesis Induced by Epstein-Barr Virus","volume":"93","author":"Saha","year":"2019","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1099\/vir.0.2008\/003392-0","article-title":"Epstein-Barr virus-encoded EBNA1 modulates the AP-1 transcription factor pathway in nasopharyngeal carcinoma cells and enhances angiogenesis in vitro","volume":"89","author":"Owen","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9870","DOI":"10.1158\/0008-5472.CAN-06-1679","article-title":"EBV latent membrane protein 1 up-regulates hypoxia-inducible factor 1alpha through Siah1-mediated down-regulation of prolyl hydroxylases 1 and 3 in nasopharyngeal epithelial cells","volume":"66","author":"Kondo","year":"2006","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Darekar, S., Georgiou, K., Yurchenko, M., Yenamandra, S.P., Chachami, G., Simos, G., Klein, G., and Kashuba, E. (2012). Epstein-Barr virus immortalization of human B-cells leads to stabilization of hypoxia-induced factor 1 alpha, congruent with the Warburg effect. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042072"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ariaans, G., Jalving, M., Vries, E.G., and Jong, S. (2017). Anti-tumor effects of everolimus and metformin are complementary and glucose-dependent in breast cancer cells. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3230-8"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1128\/MCB.01169-13","article-title":"Hypoxia-inducible factor 1 regulation through cross talk between mTOR and MT1-MMP","volume":"34","author":"Sakamoto","year":"2014","journal-title":"Mol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kraus, R.J., Yu, X., Cordes, B.A., Sathiamoorthi, S., Iempridee, T., Nawandar, D.M., Ma, S., Romero-Masters, J.C., McChesney, K.G., and Lin, Z. (2017). Hypoxia-inducible factor-1alpha plays roles in Epstein-Barr virus\u2019s natural life cycle and tumorigenesis by inducing lytic infection through direct binding to the immediate-early BZLF1 gene promoter. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006404"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jcv.2006.06.013","article-title":"Hypoxia can contribute to the induction of the Epstein-Barr virus (EBV) lytic cycle","volume":"37","author":"Jiang","year":"2006","journal-title":"J. Clin. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1128\/JVI.74.3.1101-1113.2000","article-title":"Epstein-Barr virus LMP2A-induced B-cell survival in two unique classes of EmuLMP2A transgenic mice","volume":"74","author":"Caldwell","year":"2000","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S1074-7613(00)80623-8","article-title":"Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals","volume":"9","author":"Caldwell","year":"1998","journal-title":"Immunity"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1073\/pnas.88.8.3436","article-title":"Tyrosine phosphorylation of components of the B-cell antigen receptors following receptor crosslinking","volume":"88","author":"Gold","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.virol.2003.09.017","article-title":"Epstein-Barr virus (EBV) LMP2A alters normal transcriptional regulation following B-cell receptor activation","volume":"318","author":"Portis","year":"2004","journal-title":"Virology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1158\/1541-7786.MCR-16-0305","article-title":"Comprehensive Transcriptome and Mutational Profiling of Endemic Burkitt Lymphoma Reveals EBV Type-Specific Differences","volume":"15","author":"Kaymaz","year":"2017","journal-title":"Mol. Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"17945","DOI":"10.1073\/pnas.0907994106","article-title":"Epstein-Barr virus LMP2A bypasses p53 inactivation in a MYC model of lymphomagenesis","volume":"106","author":"Bieging","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1158\/1535-7163.MCT-10-0833","article-title":"Rapamycin reverses splenomegaly and inhibits tumor development in a transgenic model of Epstein-Barr virus-related Burkitt\u2019s lymphoma","volume":"10","author":"Cen","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/jmv.25381","article-title":"Epstein-Barr virus LMP2A utilizes Syk and PI3K to activate NF-kappaB in B-cell lymphomas to increase MIP-1alpha production","volume":"91","author":"Incrocci","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4399","DOI":"10.1128\/JVI.01703-10","article-title":"Epstein-Barr virus LMP1 activates EGFR, STAT3, and ERK through effects on PKCdelta","volume":"85","author":"Kung","year":"2011","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"24157","DOI":"10.1016\/S0021-9258(18)35741-7","article-title":"The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor kappa B","volume":"267","author":"Laherty","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e01928-16","DOI":"10.1128\/JVI.01928-16","article-title":"Latent Membrane Protein 1 (LMP1) and LMP2A Collaborate To Promote Epstein-Barr Virus-Induced B Cell Lymphomas in a Cord Blood-Humanized Mouse Model but Are Not Essential","volume":"91","author":"Ma","year":"2017","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.intimp.2015.11.020","article-title":"Effects of mTOR and calcineurin inhibitors combined therapy in Epstein-Barr virus positive and negative Burkitt lymphoma cells","volume":"30","author":"Wowro","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"7047","DOI":"10.1038\/s41467-022-34890-6","article-title":"mTOR inhibition attenuates chemosensitivity through the induction of chemotherapy resistant persisters","volume":"13","author":"Liu","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1128\/JVI.78.4.1697-1705.2004","article-title":"Latent membrane protein 2A inhibits transforming growth factor-beta 1-induced apoptosis through the phosphatidylinositol 3-kinase\/Akt pathway","volume":"78","author":"Fukuda","year":"2004","journal-title":"J. Virol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:22:19Z","timestamp":1760106139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/3944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,2]]},"references-count":65,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25073944"],"URL":"https:\/\/doi.org\/10.3390\/ijms25073944","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,2]]}}}