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We recently reported genomic analyses of chronic active EBV infection (CAEBV), a proliferative disorder of T and\/or NK cells, as well as other lymphoid malignancies. We found that T and\/or NK cells undergoing clonal expansion in CAEBV patients gain somatic driver mutations as the disorder progresses. Investigation of the viral genome revealed viral genomes harboring intragenic deletions in the <jats:italic>Bam<\/jats:italic>HI\u2010rightward transcripts (BART) region and in essential lytic genes. Interestingly, we observed that these deletions resulted in leaky expression of viral lytic genes. This increased expression of viral lytic genes is reminiscent of the \u201cpre\u2010latent abortive lytic\u201d state, in which a substantial number of lytic genes are produced for weeks in the absence of progeny production, which contributes to cell survival upon de novo infection. It has been known that EBV can choose either latent or lytic state, but this dualistic concept may need to be reconsidered, as our data suggest the presence of the third, intermediate state; leaky expression of lytic genes that does not lead to completion of the full lytic amplification cycle. Leaky expression of lytic genes likely contributes to the formation and maintenance of several types of EBV\u2010associated tumors. We also presented significant circumstantial evidence suggesting that EBV infects lymphoid progenitor cells in CAEBV before differentiation into T and NK cells. Taken together, our new data shed light on oncogenesis of CAEBV and other EBV\u2010associated malignancies.<\/jats:p>","DOI":"10.1002\/rmv.2095","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T08:40:41Z","timestamp":1576572041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Oncogenesis of CAEBV revealed: Intragenic deletions in the viral genome and leaky expression of lytic genes"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-0839","authenticated-orcid":false,"given":"Takayuki","family":"Murata","sequence":"first","affiliation":[{"name":"Department of Virology and Parasitology Fujita Health University School of Medicine  Toyoake Japan"},{"name":"Department of Virology Nagoya University Graduate School of Medicine  Nagoya 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