Human herpesvirus 6 and Epstein-Barr virus in Hodgkin's disease: A controlled study by polymerase chain reaction and in situ hybridization

Guido Valente, Paola Secchiero, Paolo Lusso, Maria Cristina Abele, Cristina Jemma, Gigliola Reato, Simonetta Kerim, Robert C. Gallo, Giorgio Palestro

Research output: Contribution to journalArticle

Abstract

Human herpesvirus-6 (HHV-6), a T-lymphotropic double-stranded DNA virus highly endemic in human populations, has been suggested to play a possible role in the development of lymphoid neoplasms, especially Hodgkin's disease. To investigate this point, we evaluated the presence and distribution of HHV- 6 DNA by Southern blot, nested polymerase chain reaction, and in situ hybridization in a series of lymphoproliferative disorders including 73 Hodgkin's disease cases, 15 non-Hodgkin lymphomas, and 19 reactive lymph nodes. A high prevalence of HHV-6 infection was observed within the Hodgkin's disease category by polymerase chain reaction (38 of 52, 73%) and in situ hybridization (47 of 57, 82.4%); however, a similar prevalence was found in non-Hodgkin's lymphomas (10 of 15, 66.6%) and reactive lymph nodes (13 of 19, 68.4%). In no case did Southern blot detect vital DNA, suggesting that the neoplastic tissue contained a low number of HHV-6 copies. In situ hybridization showed that the HHV-6 positivity was restricted to lymphocytes, whereas Hodgkin and Reed-Sternberg cells were consistently negative. Immunohistochemical staining with specific monoclonal antibodies against vital structural proteins was also negative, indicating the absence of a productive infection. No relationship was observed between HHV-6 positivity and histological type, clinical parameters, and outcome of the disease. In the same series, a high proportion of cases (39 of 52, 75%) showed the presence of the Epstein-Barr virus (EBV) genome by polymerase chain reaction; in situ hybridization for Epstein-Barr-virus-encoded small RNA and immunohistochemical detection of latent membrane protein-1 gave similar results (73.6% of positive cases with both methods). In 54.9% of the cases, both sequences of HHV-6 and Epstein-Barr virus DNA were found, suggesting that a synergism of the two viruses may occur. However, the lack of detectable HHV-6 DNA in Reed-Sternberg and Hodgkin's cells seems to argue against such an interpretation. Based on these results, HHV-6 does not appear to play a specific role in the pathogenesis of Hodgkin's disease.

Original languageEnglish
Pages (from-to)1501-1510
Number of pages10
JournalAmerican Journal of Pathology
Volume149
Issue number5
Publication statusPublished - Nov 1996

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Valente, G., Secchiero, P., Lusso, P., Abele, M. C., Jemma, C., Reato, G., Kerim, S., Gallo, R. C., & Palestro, G. (1996). Human herpesvirus 6 and Epstein-Barr virus in Hodgkin's disease: A controlled study by polymerase chain reaction and in situ hybridization. American Journal of Pathology, 149(5), 1501-1510.