AUTHOR=Arai Ayako TITLE=Advances in the Study of Chronic Active Epstein-Barr Virus Infection: Clinical Features Under the 2016 WHO Classification and Mechanisms of Development JOURNAL=Frontiers in Pediatrics VOLUME=7 YEAR=2019 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2019.00014 DOI=10.3389/fped.2019.00014 ISSN=2296-2360 ABSTRACT=
Chronic active Epstein-Barr virus infection (CAEBV) is one of the Epstein-Barr virus (EBV)-positive T- or NK-lymphoproliferative diseases. It is considered rare and geographically limited to Japan and East Asia. However, CAEBV is drawing international attention, and the number of case reported worldwide is increasing, after its classification in the EBV-positive T- or NK-cell neoplasms, in the 2016 WHO classification. In this article, I review current advances in the study of CAEBV under the new definition and show future directions. In CAEBV, EBV-infected T or NK cells clonally proliferate and infiltrate multiple organs, leading to their failure. These characteristics define CAEBV as a lymphoid neoplasm. However, the main symptom of CAEBV is inflammation. Recently, the mechanisms underlying the development of CAEBV have gradually become clearer. EBV infection of T or NK cells can occur during the acute phase of primary infection with a high EBV load in the peripheral blood. In addition, it was reported that cytotoxic T cells decreased in numbers or showed dysfunction in CAEBV. These findings suggest that undetermined immunosuppressive disorders may underlie persistent infection of T or NK cells. Furthermore, EBV itself contributes to the survival of host cells.