{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:35:06Z","timestamp":1791329706975,"version":"4.3.1"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"40","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,10,3]]},"abstract":"<jats:p>\n                    Epstein\u2013Barr virus (EBV), a human herpesvirus, transforms B cell growth\n                    <jats:italic>in vitro<\/jats:italic>\n                    through expressing six virus-coded Epstein\u2013Barr nuclear antigens (EBNAs) and two latent membrane proteins (LMPs). In many EBV-associated tumors, however, viral antigen expression is more restricted, and the aetiological role of the virus is unclear. For example, endemic Burkitt lymphoma (BL) classically presents as a monoclonal, c-myc-translocation-positive tumor in which every cell carries EBV as an EBNA1-only (Latency I) infection; such homogeneity among EBV-positive cells, and the lack of EBV-negative comparators, hampers attempts to understand EBV's role in BL pathogenesis. Here, we describe an endemic BL that was unusually heterogeneous at the single-cell level and, in early passage culture, yielded a range of cellular clones, all with the same c-myc translocation but differing in EBV status. Rare EBV-negative cells were isolated alongside EBV-positive cells displaying one of three forms of restricted latency: (\n                    <jats:italic>i<\/jats:italic>\n                    ) conventional Latency I expressing EBNA1 only from a WT virus genome, (\n                    <jats:italic>ii<\/jats:italic>\n                    ) Wp-restricted latency expressing EBNAs 1, 3A, 3B, 3C, and -LP only from an EBNA2-deleted genome, and (\n                    <jats:italic>iii<\/jats:italic>\n                    ) a previously undescribed EBNA2\n                    <jats:sup>+<\/jats:sup>\n                    \/LMP1\n                    <jats:sup>\u2212<\/jats:sup>\n                    latency in which all six EBNAs are expressed again in the absence of the LMPs. Interclonal comparisons showed that each form of EBV infection was associated with a specific degree of protection from apoptosis. Our work suggests that EBV acts as an antiapoptotic rather than a growth-promoting agent in BL by selecting among three transcriptional programs, all of which, unlike the full virus growth-transforming program, remain compatible with high c-myc expression.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0509988103","type":"journal-article","created":{"date-parts":[[2006,9,25]],"date-time":"2006-09-25T21:03:54Z","timestamp":1159218234000},"page":"14935-14940","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":129,"title":["Three restricted forms of Epstein\u2013Barr virus latency counteracting apoptosis in c-myc-expressing Burkitt lymphoma cells"],"prefix":"10.1073","volume":"103","author":[{"given":"Gemma L.","family":"Kelly","sequence":"first","affiliation":[{"name":"Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United 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