Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection

Unusual Epstein-Barr virus (EBV) infection into T or natural killer cells p lays a pivotal role in the pathogenesis of acute EBV-associated hemophagocy tic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). The precise frequency and localization of EBV genome in lymphocyte subpopu lations especially within T-cell subpopulations are unclear in these EBV-re lated disorders. This study analyzed the frequency of EBV-infected cells in circulating lymphocyte subpopulations from 4 patients with acute EBV-HLH a nd 4 with CAEBV. EBV-encoded small RNA-1 in situ hybridization examination of peripheral blood lymphocytes showed a significantly higher frequency of EBV-infected cells of 1.0% to 13.4% in EBV-HLH and 1.6% to 25.6% in CAEBV, respectively. The patterns of EBV infection in lymphocyte subpopulations we re quite different between acute EBV-HLH and CAEBV. EBV infection was predo minant in CD8(+) T cells in all EBV-HLH patients, whereas the dominant EBV- infected cell populations were non-CD8(+) lymphocyte subpopulations in CAEB V patients. Phenotypical analysis revealed that EBV-infected cell populatio ns from both EBV-HLH and CAEBV were activated. There was no predominance of any EBV substrain of latent membrane protein-1, EBV-associated nuclear ant igen (EBNA)-1, and EBNA-2 genes between the 2 abnormal EBV-associated disor ders, and self-limited acute infectious mononucleosis. These results showin g differential virus-cell interactions between acute EBV-HLH and CAEBV indi cated different pathogenic mechanisms against EBV infection between the 2 E BV-associated diseases, which accounts for the difference in clinical manif estations between the 2 diseases.