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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1882-1888
IMMUNOBIOLOGY
Differential cellular targets of Epstein-Barr virus (EBV)
infection between acute EBV-associated hemophagocytic
lymphohistiocytosis and chronic active EBV infection
Yoshihito Kasahara,
Akihiro Yachie,
Kenkichi Takei,
Chiharu Kanegane,
Kanae Okada,
Kazuhide Ohta,
Hidetoshi Seki,
Noboru Igarashi,
Keiko Maruhashi,
Keita Katayama,
Eiji Katoh,
Gaku Terao,
Yukio Sakiyama, and
Shoichi Koizumi
From the Department of Pediatrics, Angiogenesis and
Vascular Development, Graduate School of Medical Science, and the
Department of Laboratory Sciences and Department of Nursing, School of
Health Sciences, Faculty of Medicine, Kanazawa University, Ishikawa,
Japan; Department of Pediatrics, Toyama Prefectural Central Hospital,
Toyama, Japan; Department of Pediatrics, Fukui Saiseikai Hospital,
Fukui, Japan; Department of Pediatrics, Fukui Prefectural Hospital,
Fukui, Japan; and Department of Human Gene Therapy, Graduate School of
Medicine, Hokkaido University, Sapporo, Japan.
Unusual Epstein-Barr virus (EBV) infection into T or natural killer
cells plays a pivotal role in the pathogenesis of acute EBV-associated
hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV
infection (CAEBV). The precise frequency and localization of EBV genome
in lymphocyte subpopulations especially within T-cell subpopulations
are unclear in these EBV-related disorders. This study analyzed the
frequency of EBV-infected cells in circulating lymphocyte
subpopulations from 4 patients with acute EBV-HLH and 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 were quite different between acute EBV-HLH and CAEBV.
EBV infection was predominant in CD8+ T cells in all
EBV-HLH patients, whereas the dominant EBV-infected cell populations
were non-CD8+ lymphocyte subpopulations in CAEBV patients.
Phenotypical analysis revealed that EBV-infected cell populations from
both EBV-HLH and CAEBV were activated. There was no predominance of any
EBV substrain of latent membrane protein-1, EBV-associated nuclear antigen (EBNA)-1, and EBNA-2 genes between the 2 abnormal
EBV-associated disorders, and self-limited acute infectious
mononucleosis. These results showing differential virus-cell
interactions between acute EBV-HLH and CAEBV indicated different
pathogenic mechanisms against EBV infection between the 2 EBV-associated diseases, which accounts for the difference in clinical
manifestations between the 2 diseases.
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