Expression of Epstein-Barr virus in Langerhans' cell histiocytosis.
Langerhans' cell histiocytosis (LCH) is a proliferative histiocytic disorder of unknown etiology. We previously reported that Epstein-Barr virus (EBV) infects and proliferates in macrophages, and investigated the possibility that EBV exhibits etiologic effects in LCH. To detect EBV expression, paraffin sections from 17 LCH cases were examined by mRNA in situ hybridization for EBV BamHIW, Epstein-Barr virus nuclear antigen-2 (EBNA2), and Epstein-Barr virus-encoded small nonpolyadenylated RNA (EBER1) sequences, and by indirect immunofluorescence staining for EBNA2, latent membrane protein 1 (LMP1), and BamHIZ-coding leftward-reading frame 1 (BZLF1). To detect EBV DNA, polymerase chain reaction (PCR)-Southern blotting was used. All cases showed positive hybridization signals by BamHIW mRNA in situ hybridization. Also, 13 and 14 cases showed positive signals for EBNA2 and EBER1 RNA in situ hybridization, respectively. Furthermore, almost all cases exhibited fluorescence after immunofluorescence staining with monoclonal anti-EBNA2 and anti-BZLF1 antibodies, and 15 cases were positive after treatment with monoclonal anti-LMP1 antibody. PCR-Southern blotting detected an amplified EBER1 sequence in all 9 cases examined. EBV expression was confirmed in LCH using in situ hybridization and immunofluorescence. Furthermore, EBV DNA was also detected by PCR-Southern blotting. These positive results of BZLF1 suggest that EBV replicates in LCH tissues.
Shimakage
Misuzu
M
Clinical Research Institute, Osaka National Hospital, Osaka, Japan.
Sasagawa
Toshiyuki
T
Kimura
Michio
M
Shimakage
Tatsuya
T
Seto
Shiro
S
Kodama
Ken
K
Sakamoto
Haruhiko
H
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000473:pathology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006646:Histiocytosis, Langerhans-Cell / Q000473:pathology / Q000821:virology*; D006801:Humans; D017403:In Situ Hybridization; D007223:Infant; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis
D004279:DNA, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; C099537:Epstein-Barr virus encoded RNA 1; D012333:RNA, Messenger; D012367:RNA, Viral