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 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.
Kasahara
Y
Y
Department of Pediatrics, Angiogenesis and Vascular Development, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan. ykasa@ped.m.kanazawa-u.ac.jp
Yachie
A
A
Takei
K
K
Kanegane
C
C
Okada
K
K
Ohta
K
K
Seki
H
H
Igarashi
N
N
Maruhashi
K
K
Katayama
K
K
Katoh
E
E
Terao
G
G
Sakiyama
Y
Y
Koizumi
S
S
D000208:Acute Disease; D001402:B-Lymphocytes / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D002675:Child, Preschool; D002908:Chronic Disease; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000821:virology*; D005260:Female; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D015616:Histiocytosis, Non-Langerhans-Cell / Q000276:immunology / Q000821:virology*; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D007694:Killer Cells, Natural / Q000821:virology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis
C099537:Epstein-Barr virus encoded RNA 1; D012367:RNA, Viral