Does Simian Virus 40 Cause Non-Hodgkin Lymphoma? A Review of the Laboratory and Epidemiological Evidence

Engels, Eric A.

doi:10.1080/07357900500202820

Cited by 12 publications

(7 citation statements)

References 30 publications

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“…The debate on the possible adverse effects of SV40 for humans has been contentious 9, 10, 11, 12, 13, 14, 15, 16, 17, 18. High rates of recovery of SV40 DNA sequences from cancer tissues have led some investigators to propose that SV40 infection may have a role in the development of mesothelioma, brain tumors, osteosarcoma and NHL.…”

Section: Introductionmentioning

confidence: 99%

SV40 and human cancer: A review of recent data

Shah

2006

Intl Journal of Cancer

108

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An unknown proportion of formalin-inactivated poliovirus vaccine lots administered to millions of US residents between 1955 and 1963 was contaminated with small amounts of infectious simian virus 40 (SV40), a polyomavirus of the rhesus macaque. It has been reported that mesothelioma, brain tumors, osteosarcoma and non-Hodgkin lymphoma (NHL) contain SV40 DNA sequences and that SV40 infection introduced into humans by the vaccine probably contributed to the development of these cancers. The Immunization Safety Review Committee of the Institute of Medicine (IOM) reviewed this topic in 2002. The present review of recent studies showed that the earlier results describing the recovery of SV40 DNA sequences from a large proportion of the above tumors were not reproducible and that most studies were negative. Contamination with laboratory plasmids was identified as a possible source of false positive results in some previous studies. The low-level immunoreactivity of human sera to SV40 was very likely the result of cross-reactivity with antibodies to the SV40-related human polyomaviruses BKV and JCV, rather than of authentic SV40 infection. SV40 sero-reactivity in patients with the suspect tumors was no greater than that in controls. In epidemiologic studies, the increased incidence of some of the suspect tumors in the 1970s to 1980s was not related to the risk of exposure to SV40-contaminated vaccines. In summary, the most recent evidence does not support the notion that SV40 contributed to the development of human cancers. 1 The committee recommended the development and use of sensitive and specific serologic tests for Simian virus 40 (SV40), the development and use of sensitive and specific standardized techniques for SV40 detection, and the study of the transmissibility of SV40 in humans.1 This review presents the perspective of the author who has investigated this question since the mid 1960s.2 The background of the problem is provided first and the discussion is centered primarily on studies published in 2002 and later, in order to evaluate the evidence for an etiologic role of SV40 infection for human cancer. Earlier data are referred to for context and when necessary to make a point. Three questions are addressed: (i) some of the earlier studies reported SV40 DNA sequences (and to a lesser extent SV40 T antigen) in large proportions of mesothelioma, brain tumors, osteosarcoma and non-Hodgkin lymphoma (NHL). Are these results reproducible in the most recent studies? (ii) serology is an independent marker for viral exposure. Is there serological evidence that SV40 is circulating in the human communities or that patients with the suspect cancers are more frequently exposed to SV40? and (iii) the incidence of mesothelioma, brain tumors and NHL increased in the decades following human exposure to SV40 in the contaminated vaccines. Are these 2 events related?Background

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Section: Introductionmentioning

confidence: 99%

SV40 and human cancer: A review of recent data

Shah

2006

Intl Journal of Cancer

108

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“…28 In vitro experiments have shown that SV40 large T antigens promote transformation by binding and inactivating the products of several tumor suppressor genes, particularly P53. 28,29 Despite these suggestions of a possible link between SV40 and P53 accumulation, no previous studies have investigated the potential implication of the SV40 in such accumulation of P53 protein in diffuse large B-cell lymphomas.…”

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confidence: 99%

Presence of simian virus 40 in diffuse large B-cell lymphomas in Tunisia correlates with germinal center B-cell immunophenotype, t(14;18) translocation, and P53 accumulation

et al. 2008

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Previously we have reported the presence of simian virus 40 DNA in 56% of diffuse large B-cell lymphomas in Tunisia. Here, we investigated the relationship between the status of simian virus 40 and t(14;18) translocation, germinal center status, and P53 and BCL2 expression to assess the clinical and biological relevance of simian virus 40 presence in diffuse large B-cell lymphomas. Therefore, we evaluated by immunohistochemistry the expression patterns of CD10, BCL6, MUM1, BCL2, and P53 in 86 diffuse large B-cell lymphomas (48 simian virus 40-positive and 38 simian virus 40-negative cases). The t(14;18) translocation was investigated by polymerase chain reaction. Immunostaining patterns for CD10, BCL6, and MUM1 were used to subclassify diffuse large B-cell lymphoma cases as germinal center or non-germinal center phenotypes. Germinal center phenotype, t(14;18), P53, and BCL2 expression were found in 71, 30, 55, and 65% of cases, respectively. Interestingly, germinal center phenotype, t(14;18), and P53 accumulation were found to be more frequent in simian virus 40-positive cases than in simian virus 40-negative ones (81, 44, 69 vs 58, 13, 37%; P ¼ 0.018, 0.002, and 0.003, respectively). However, there were no correlations between the presence of simian virus 40 and the expression of CD10, BCL6, MUM1 and BCL2, patient's age and gender, clinical stage, or the International Prognosis Index. Multivariate logistic regression analyses revealed that the germinal center phenotype, P53 accumulation, and t(14;18) were independent factors for simian virus 40 association (P ¼ 0.029, 0.006, and 0.014, respectively). There were no significant differences in overall survival regarding P53, BCL2, or t(14;18) status. However, patients with germinal center phenotype or low International Prognosis Index scores displayed a significantly better survival than those with non-germinal center phenotype or high International Prognosis Index scores (P ¼ 0.003 and 0.0001, respectively). These two prognosis factors remain independent in multivariate analyses (P ¼ 0.001 and o0.0001, respectively). Interestingly, among patients with germinal center phenotype, simian virus 40-positive subgroup displayed a significantly shorter survival than simian virus 40-negative subgroup (P ¼ 0.034). In summary, these findings support a role of simian virus 40 in the pathogenesis of diffuse large B-cell lymphomas. On other hand, they suggest that a significant proportion of diffuse large B-cell lymphoma cases with germinal center phenotype may result from early transformation by simian virus 40, mainly those harboring the t(14;18).

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“…Some groups indicated an association between NHL and SV40 by reporting a high prevalence of SV40 Tag coding sequences at up to 43% [1][2][3]. Other investigators have not confirmed the association [6]. Differing prevalence levels of SV40 infection, detected in human populations of distinct origin, could be due to living parameters and hygiene conditions [7].…”

Section: Introductionmentioning

confidence: 99%

High prevalence of antibodies reacting to mimotopes of Simian virus 40 large T antigen, the oncoprotein, in serum samples of patients affected by non-Hodgkin lymphoma

Mazzoni

Pietrobon

Bilancia

et al. 2017

Cancer Immunol Immunother

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A new immunological investigation was carried out to study the association between non-Hodgkin lymphoma and Simian virus 40 (SV40). To this end, a new indirect ELISA was employed with two mimotopes from SV40 large T antigen (Tag), the viral oncoprotein, to analyse for specific reactions to antibodies in sera from non-Hodgkin lymphoma patients and controls, represented by healthy subjects (HS) and breast carcinoma (BC) patients. This study allowed us to assay a new sera collection from non-Hodgkin lymphoma patients (NHL, n = 254). To verify the association between NHL and SV40 Tag, two totally independent cohorts were analysed: NHL1 n = 150 and NHL2 n = 104. The epidemiological survey included sera from HS1, n = 150; HS2, n = 104 and BC, n = 78. This new indirect ELISA revealed that antibodies against SV40 Tag mimotopes are detectable in NHL1 and NHL2 sera with a prevalence of 37 and 36%, respectively. The prevalence of SV40-antibodies detected in both NHL1 and NHL2 cohorts differs statistically from controls, at 19% for HS1 (p < 0.01), HS2 (p < 0.05) and BC patients (p < 0.05). This study, carried out with an immunological assay with specific Tag oncoprotein mimotopes of Simian virus 40, reports the presence of IgG antibodies against the large Tumour antigen in non-Hodgkin lymphomas for the first time. Our immunological data with two independent NHL cohorts show a statistically significant association between Simian virus 40 Tag and non-Hodgkin lymphoma. These results suggest that SV40-positive non-Hodgkin lymphomas could be treated differently from those tested SV40-negative.

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Does Simian Virus 40 Cause Non-Hodgkin Lymphoma? A Review of the Laboratory and Epidemiological Evidence

Cited by 12 publications

References 30 publications

SV40 and human cancer: A review of recent data

SV40 and human cancer: A review of recent data

Presence of simian virus 40 in diffuse large B-cell lymphomas in Tunisia correlates with germinal center B-cell immunophenotype, t(14;18) translocation, and P53 accumulation

High prevalence of antibodies reacting to mimotopes of Simian virus 40 large T antigen, the oncoprotein, in serum samples of patients affected by non-Hodgkin lymphoma

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