A defective, rearranged Epstein-Barr virus genome in EBER-negative and EBER-positive Hodgkin's disease.
A ubiquitous herpesvirus that establishes life-long infection, the Epstein-Barr virus (EBV) has yielded little insight into how a single agent in general accord with its host can produce diverse pathologies ranging from oral hairy leukoplakia to nasopharyngeal carcinoma, from infectious mononucleosis to Hodgkin's disease (HD) and Burkitt's lymphoma. Its pathogenesis is further confounded by the less than total association of virus with histologically similar tumors. In other viral systems, defective (interfering) viral genomes are known to modulate outcome of infection, with either ameliorating or intensifying effects on disease processes initiated by prototype strains. To ascertain whether defective EBV genomes are present in HD, we examined paraffin-embedded tissue from 56 HD cases whose EBV status was first determined by cytohybridization for nonpolyadenylated EBV RNAs (EBERs). Using both standard polymerase chain reaction (PCR) and PCR in situ hybridization, we successfully amplified sequences that span abnormally juxtaposed BamHI W and Z fragments characteristic of defective heterogeneous (het) EBV DNA from 10 of 32 (31%) EBER-positive tumors. Of 24 EBER-negative HD, 8 yielded PCR products indicating presence of het EBV DNA. Two of these contained defective EBV in the apparent absence of the prototype virus. Of the 42 tumors analyzed for defective EBV by both PCR techniques, there was concordance of results in 38 (90%). Detection of defective EBV genomes with the potential to disrupt viral gene regulation suggests one mechanism for pathogenic diversity that may also account for loss of prototypic EBV from individual tumor cells.
Gan
Yan-Jun
YJ
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Razzouk
Bassem I
BI
Su
Tao
T
Sixbey
John W
JW
D000328:Adult; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000821:virology*; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000235:genetics / Q000821:virology*; D006801:Humans