Differential cellular susceptibility to Epstein-Barr virus infection in a patient with X-linked lymphoproliferative disease

Epstein-Barr virus (EBV) is often associated with lethal lymphoproliferative diseases in immunologically compromised individuals. Recently, we have studied a 20-month-old boy with X-linked lymphoproliferative disease (XLP) who had succumbed to infectious mononucleosis (IM) complicated by fulminant hepatitis and virus-associated hemophagocytic syndrome following EBV infection. EBV genomes were detected in peripheral blood lymphocytes (PBL), cervical and mesenteric lymph nodes, liver, spleen, thymus, and bone marrow. According to restriction endonuclease analyses, the EBV-DNA pattern was similar in all samples except for the EBV-DNA from the bone marrow. Additionally, circular EBV-DNA (suggesting a latent infection) predominated in spontaneously established lymphoblastoid cell lines (LCLs) derived from both the lymph node and cord lymphocytes co-cultured with PBL. In contrast, both circular and linear EBV-DNA (suggesting a lytic infection) were noted in spontaneously established LCLs derived from his PBL. Furthermore, LCLs derived from both the lymph node and cord lymphocytes co-cultured with PBL expressed fewer reactive cells for early antigen (EA) and viral capsid antigen (VCA) than spontaneous LCLs from his PBL, thus providing evidence for different B cellular susceptibility to EBV infection in this patient with XLP. Finally, defective EBV-specific cytotoxic T cell activity was observed in this patient. Latent EBV infected cells may easily escape immunosurveillance by the host. These findings may explain the fatal course of EBV infection in this patient.