Demonstration of Epstein-Barr virus replication in Reed-Sternberg cells of Hodgkin's disease.
Epstein-Barr virus (EBV) is detectable in approximately 40% of cases of Hodgkin's disease (HD). The viral genomes remain latent but positive staining with anti-ZEBRA antibody in a small fraction of Reed-Sternberg (RS) cells of some cases of HD would suggest possible activation of EBV replication within these cells. We report the investigation of 40 cases of EBV-associated HD (including 5 human immunodeficiency virus [HIV]-positive cases) using anti-ZEBRA antibodies. Positive staining was found in only three (HIV-negative) cases. One of these three cases showed approximately 1% of ZEBRA-positive tumor cells, whereas the other two cases showed rare positive cells. In the case with 1% ZEBRA-positive cells, a strong signal was obtained with anti-EA-R antibody and BHLF1 oligoprobes, which indicated early gene expression. EBV replication could be shown in this case by nonisotopic in situ DNA-DNA hybridization, which showed markedly increased numbers of EBV genomes in a few RS cells. Viral replication was confirmed using reverse transcriptase and polymerase chain reaction that detected transcripts from the BLLF1 gene encoding for the membrane antigen gp350/220. EBV replication in RS cells seems to be an exceptional event but may provide clues to mechanisms of control of viral latency and assume clinical implications in the future.
Laboratoire d'Anatomie Pathologique, CHU Purpan, Toulouse, France.
P
P
Brousset
H
H
Knecht
B
B
Rubin
E
E
Drouet
S
S
Chittal
F
F
Meggetto
T A
TA
Saati
E
E
Bachmann
G
G
Denoyel
A
A
Sergeant
D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D015870:Gene Expression; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000254:growth & development*; D006689:Hodgkin Disease / Q000382:microbiology*; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D016539:Reed-Sternberg Cells / Q000382:microbiology*; D015678:Viral Structural Proteins / Q000235:genetics; D014779:Virus Replication
D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012367:RNA, Viral; D015678:Viral Structural Proteins