Lack of association of polyomavirus and herpesvirus types 6 and 7 in human lymphomas

Abstract

BACKGROUND The association of viruses with several human tumors has been studied for almost 100 years, and it remains a very controversial issue. Due to the fact that the presence of polyomaviruses and herpes viruses reportedly are associated with lymphomas, albeit with striking results and differences between the many studies, the authors undertook a study into the presence of viral sequences of polyomavirus (BK virus, JC virus, and especially simian virus 40 [SV40]) in human lymphomas in an attempt to explain this contradictory association. To complete the study, the presence of different virus types from the herpesviriridae family were analyzed, such as herpesvirus type 6 (HHV6), HHV7, HHV8, and Epstein–Barr virus, in human lymphomas. METHODS DNA was isolated from 83 frozen human lymphoma samples, and different polymerase chain reaction techniques were used to find polyomavirus and herpesvirus sequences in these samples. To assess the incidence of the presence of sequences in lymphomas, a parallel analysis was made of 53 samples from normal donor spleen lymphocytes. Positive samples were analyzed for polyomavirus sequences by immunohistochemistry. RESULTS Polyomavirus sequences were detected in 9 of 83 lymphomas (11%), and SV40 sequences could be confirmed in only 1 lymphoma. Immunohistochemistry for large‐T antigen was negative in all samples. Herpesviruses were detected in 53 of 83 lymphomas (63.9%), were detected more frequently in Hodgkin lymphomas (80%) than in non‐Hodgkin lymphomas (58.7%), and were detected in > 60% of normal spleen lymphocytes. CONCLUSIONS The current results did not support a clear association of polyomavirus and HHV6 or HHV7 with lymphomas; HHV6 and HHV7 sequences were detected in a similar percentage of normal samples and lymphomas. The lack of significant differences between normal and malignant lymphocytes and the absence of viral protein expression in the tumor cells did not allow the establishment of a clinical correlation between polyomaviruses or HHVs (HHV6, HHV7, HHV8) and lymphomas. Nevertheless, because viral products can be lost during tumor progression, and because host factors can modulate the oncogenic role of some viruses, the hypothetical role of these viruses cannot be discarded completely. Cancer 2005. © 2004 American Cancer Society.

BK virus and human cancer: Innocent until proven guilty

“…Since BKV has been convincingly detected in peripheral blood cells of normal individuals [30,32,128], investigators began to look for an association between BKV and lymphoma. Only 5 out of 83 lymphoma samples were positive for BKV DNA using standard and real-time PCR [129]. Based on the higher percentage of normal BKV-positive lymphocytes routinely observed, this study does not support an association between BKV and lymphoma [30,32,128].…”

Prediagnostic Circulating Antibodies to JC and BK Human Polyomaviruses and Risk of Non-Hodgkin Lymphoma

“…Three studies that were primarily investigations of SV40 in lymphoma tissues detected no JCV or BKV DNA sequences in NHL tissues (20)(21)(22). Another laboratory reported JCV and BKV sequences in 5% and 6% of 83 lymphomas, respectively (18). Finally, a report of JCV DNA sequences identified 81% of 27 central nervous system lymphomas analyzed (19).…”

“…JCV has been shown to infect B-lymphocytes (14,15), and Neel and colleagues have described chromosomal damage in lymphocytes associated with both JCV (16,17) and BKV (16) infections. Some investigators have detected polyomavirus sequences from NHL tissues, including one laboratory that detected JCV and BKV sequences in 5% and 6% of 83 lymphomas, respectively (18) and a recent report that showed the presence of JCV DNA sequences in 22 of 27 B-cell lymphomas of the central nervous system, a subset of which also contained EBV DNA (19).…”

SV40 association with human malignancies and mechanisms of tumor immunity by large tumor antigen

“…Using data from serological experiments, a number of investigators have demonstrated a lack of significant SV40 seroprevalence in patients with NHL [71][72][73][74]. Though these noted studies [71][72][73][74] relied solely on serological evidence, PCR has been used to show that SV40 DNA sequences were either of low incidence in comparison to controls or unable to be detected in NHL samples from a variety of countries, including the United States [75][76][77][78][79].…”