EBV in T-/NK-Cell Tumorigenesis

  • Hiroshi KimuraEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1045)


Epstein–Barr virus (EBV), which is associated with B-cell proliferative disorders, also transforms T- or natural killer (NK)-lineage cells and has been connected with various T- or NK (T/NK)-cell malignancies, such as extranodal NK/T-cell lymphoma-nasal type and aggressive NK-cell leukemia. Chronic active EBV (CAEBV) disease, which occurs most often in children and young adults in East Asia, is an EBV-associated T-/NK-cell lymphoproliferative disease. Patients with CAEBV often progress to overt lymphoma or leukemia over a long-term clinical course. EBV’s transforming capacity in B cells is well characterized, but the molecular pathogenesis of clonal expansion caused by EBV in T/NK cells has not yet been clarified. In the primary infection, EBV infects B cells and epithelial cells and may also infect some T/NK cells. In some individuals, because of poor presentation by specific human leukocyte antigens or the genetic background, EBV-infected T/NK cells evade host immunity and survive. Occasionally, with the help of viral oncogenes, EBV-associated T/NK lymphoproliferative diseases, such as CAEBV, may develop. The subsequent accumulation of genetic mutations and/or epigenetic modifications in driver genes, such as DDX3X and TP53, may lead to overt lymphoma and leukemia. Activation-induced cytidine deaminase and the APOBEC3 family, driven by EBV infection, may induce chromosomal recombination and somatic mutations.


AID CAEBV Chronic active EBV disease DDX3X ENKL Extranodal NK/T-cell lymphoma-nasal type EBV-T/NK LPD Lymphomagenesis Lymphoproliferative disease 


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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of VirologyNagoya University Graduate School of MedicineNagoyaJapan

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