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Infrequently, EBV infection causes infectious mononucleosis (IM) or Burkitt lymphoma (BL). Type I EBV infection, particularly type I BL, stimulates strong responses of innate immune cells. Humans respond to EBV in two alternative ways. Of 24 individuals studied, 13 made strong NK and \u03b3\u03b4 T cell responses, whereas 11 made feeble \u03b3\u03b4 T cell responses but stronger NK cell responses. The difference does not correlate with sex, HLA type, or previous exposure to EBV or cytomegalovirus. Cohorts of EBV+ children and pediatric IM patients include both group 1 individuals, with high numbers of \u03b3\u03b4 T cells, and group 2 individuals, with low numbers. The even balance of groups 1 and 2 in the human population points to both forms of innate immune response to EBV having benefit for human survival. Correlating these distinctive responses with the progress of EBV infection might facilitate the management of EBV-mediated disease.<\/jats:p>","DOI":"10.1084\/jem.20161017","type":"journal-article","created":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T14:10:15Z","timestamp":1493820615000},"page":"1827-1841","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":78,"title":["Two alternate strategies for innate immunity to Epstein-Barr virus: One using NK cells and the other NK cells and \u03b3\u03b4 T cells"],"prefix":"10.1084","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9583-8487","authenticated-orcid":true,"given":"Zakia","family":"Djaoud","sequence":"first","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 1"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1301-8301","authenticated-orcid":true,"given":"Lisbeth A.","family":"Guethlein","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 1"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Horowitz","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 1"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3490-2419","authenticated-orcid":true,"given":"Tarik","family":"Azzi","sequence":"additional","affiliation":[{"name":"Experimental Infectious Disease and Cancer Research, Children\u2019s Research Center, University Children\u2019s Hospital of Zurich, 8032 Zurich, Switzerland 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neda","family":"Nemat-Gorgani","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 1"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-4113","authenticated-orcid":true,"given":"Daniel","family":"Olive","sequence":"additional","affiliation":[{"name":"Team Immunity and Cancer, Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U1068; Centre National de la Recherche Scientifique, UMR7258, Institut Paoli-Calmettes; Aix-Marseille University, UM 105, 13284 Marseille, France 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2712-1374","authenticated-orcid":true,"given":"David","family":"Nadal","sequence":"additional","affiliation":[{"name":"Experimental Infectious Disease and Cancer Research, Children\u2019s Research Center, University Children\u2019s Hospital of Zurich, 8032 Zurich, Switzerland 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-7703","authenticated-orcid":true,"given":"Paul J.","family":"Norman","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 1"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"M\u00fcnz","sequence":"additional","affiliation":[{"name":"Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8006 Zurich, Switzerland 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Parham","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 1"},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,5,3]]},"reference":[{"key":"2023072604032888800_bib1","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/nbt.2594","article-title":"viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia","volume":"31","author":"Amir","year":"2013","journal-title":"Nat. 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