Chronic active EB virus infection

Abstract

 Chronic active EB virus infection is an intractable disease. EBV latently infects T cells or NK cells, proliferates in a clonal manner, infiltrates organs, and triggers various symptoms. The prognosis is generally poor; in the absence of treatment, organ complications and a blast crisis often cause death. Recently, we performed a large-scale, comprehensive genetic analysis of patients with chronic active EB virus infection, and found: 1) it is unlikely that any primary immunodeficiency is in play (because mutations in germ cell sequences were rarely observed); 2) EBV-infected cells contained mutations in driver genes such as DDX3X and KMT2D and, in cases that could be observed over time, clonal evolution of EBV-infected cells was evident; and, 3) defective EBV was frequently observed and may be involved in disease onset. This review outlines the pathology of chronic active EB virus infection revealed by our genetic analyses, and the latest views on optimal diagnosis and treatment.