{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:44:18Z","timestamp":1790804658743,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Protocols"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The oncogenic Epstein Barr virus (EBV) is an exclusively human pathogen with related lymphocryptoviruses (\u03b31\u2010herpesviruses) only present in monkeys. Therefore, experimentation with EBV infection in a small animal model requires reconstitution or adoptive transfer of human lymphocyte populations, primarily EBV's main host cell, the human B cell. In this protocol we describe human immune system reconstitution after neonatal transfer of CD34\n                    <jats:sup>+<\/jats:sup>\n                    hematopoietic progenitor cells in lymphodeplete immune compromised mouse strains, using NOD\u2010\n                    <jats:italic>scid<\/jats:italic>\n                    \u03b3\n                    <jats:sub>c<\/jats:sub>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    (NSG) mice as a commonly used example. Such reconstituted humanized mice allow intraperitoneal and intranasal infection with EBV and we describe injection of 10\n                    <jats:sup>5<\/jats:sup>\n                    infectious particles of the prototypic EBV strain B95\u20108 that can be produced from a recombinant bacmid (p2089) in HEK293 cells. Infection with this dose mimics symptomatic primary EBV infection, infectious mononucleosis (IM), with high viral loads plateauing 4 weeks after infection, with CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell lymphocytosis at week 5 and 6 after infection. This IM\u2010like primary EBV infection in humanized mice leads to clonal EBV\u2010induced B\u2010cell lymphoproliferations that resemble large B\u2010cell lymphomas with the latency III program of EBV infection. We describe Basic Protocols to monitor viral loads, immunohistochemistry of infected tissues and spectral flow cytometry to characterize protective T\u2010cell expansion. The described mouse model has been used by us and others to characterize mutant EBV infections, cell\u2010mediated immune control of EBV, modulation of EBV pathogenesis by co\u2010infections with human immunodeficiency virus (HIV) and Kaposi sarcoma associated herpesvirus (KSHV), as well as passive transfer of vaccine elicited antibodies to test their protection against EBV infection. \u00a9 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 1<\/jats:bold>\n                    : CD34\n                    <jats:sup>+<\/jats:sup>\n                    human hematopoietic progenitor cell isolation and characterization\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 2<\/jats:bold>\n                    : Human immune system reconstitution and characterization\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 3<\/jats:bold>\n                    : Recombinant EBV production and humanized mouse infection\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 4<\/jats:bold>\n                    : Viral load quantification, lymphoma assessment, and immunohistochemistry after EBV infection of humanized mice\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Basic Protocol 5<\/jats:bold>\n                    : Human T\u2010cell response analysis after EBV infection of humanized mice\n                  <\/jats:p>","DOI":"10.1002\/cpz1.70257","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:44:31Z","timestamp":1764067471000},"source":"Crossref","is-referenced-by-count":4,"title":["Humanized Mouse Models of Epstein Barr Virus Infection"],"prefix":"10.1002","volume":"5","author":[{"given":"Saskia Gertrud","family":"von Boxberg","sequence":"first","affiliation":[{"name":"Viral Immunobiology, Institute of Experimental Immunology University of Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Gehrmann","sequence":"additional","affiliation":[{"name":"Viral Immunobiology, Institute of Experimental Immunology University of Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja Luisa","family":"Nopper","sequence":"additional","affiliation":[{"name":"Viral Immunobiology, Institute of Experimental Immunology University of Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Romann","sequence":"additional","affiliation":[{"name":"Viral Immunobiology, Institute of Experimental Immunology University of Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"K\u00f6segi","sequence":"additional","affiliation":[{"name":"Viral Immunobiology, Institute of Experimental Immunology University of Z\u00fcrich  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-1940","authenticated-orcid":false,"given":"Christian","family":"M\u00fcnz","sequence":"additional","affiliation":[{"name":"Viral 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Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004333"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008477"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109056"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201049209\u2010w"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007748"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv114"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.11.041"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142905.hga03cs00"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.08.026"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8245"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.9.5188"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009482"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathmechdis\u2010012418\u2010013023"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018025536"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(88)90028\u20101"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.173489"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010025\u201009378\u20100"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI86923"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01512\u201010"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76357"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.241.4873.1632"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.06.009"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202000640"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1431"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579\u2010025\u201001181\u2010y"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007039"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01941\u201018"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.232381299"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.24288"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000475107"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708662"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081720"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010032414\u2010112326"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093933"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14380"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.09.012"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.614876"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58092"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202048655"}],"container-title":["Current 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