Lack of Serologic Evidence for Prevalent Simian Virus 40 Infection in Humans

Carter, Joseph J.; Madeleine, Margaret M.; Wipf, Greg C.; Garcea, Robert L.; Pipkin, P.A.; Minor, Philip D.; Galloway, Denise A.

doi:10.1093/jnci/djg074

Cited by 107 publications

(117 citation statements)

References 26 publications

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“…46 Carter et al, using a VLP-based ELISA found 6.6% SV40 seroprevalence, but none of the positive reactions remained after competition with BKV or JCV VLP. 25 In accordance with this, in the present study only 5 positive samples remained when all previously positive samples and a selection of negative samples were retested in a neutralization assay, and none of these could neutralize SV40 when BKV/JCV was blocked.…”

Section: Discussionsupporting

confidence: 70%

“…Recently published studies have shown that SV40 reactivity in human sera may be almost entirely a result of cross-reactivity with BKV and JCV antibodies. 24,25,46 Also in the present study, when SV40 VP1 antibodies were measured in the antibody capture assay without precautions to suppress crossreactive BKV and JCV VP1 antibodies they were correlated with BKV and/or JCV VP1 responses.…”

Section: Discussionsupporting

confidence: 53%

“…Several studies of recently collected sera from age groups probably vaccinated with SV40-contaminated preparations also have not found high-titre SV40. 21,25,46,[49][50][51] It should be noted, however, that all comparisons with previous serological results might be dubious because of the difficulties encountered with cross-reactivity of antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…23 Results of old and recent studies are thus difficult to compare because of use of different assay principles and varying sensitivities. Serological studies published so far on antibodies to SV40 among cancer patients and their controls have indicated low prevalence of antibodies to SV40, 25 and a lack of association between cancer risk and the presence of antibodies to viral proteins when measured both at the time of diagnosis 26,27 and prior to diagnosis. 28 The interpretation of the repeated finding of SV40 in human tumors is controversial.…”

mentioning

confidence: 99%

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Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples

Kjærheim

Røe

Waterboer

et al. 2007

Intl Journal of Cancer

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The rhesus monkey virus Simian Virus 40 (SV40) is a member of the polyomavirus family. It was introduced inadvertently to human populations through contaminated polio vaccine during the years [1956][1957][1958][1959][1960][1961][1962][1963], can induce experimental tumors in animals and transform human cells in culture. SV40 DNA has been identified in mesothelioma and other human tumors in some but not all studies. We tested prediagnostic sera from 49 mesothelioma cases and 147 matched controls for antibodies against the viral capsid protein VP1 and the large T antigen of SV40 and of the closely related human polyomaviruses BK and JC, and for SV40 DNA. Cases and controls were identified among donors to the Janus Serum Bank, which was linked to the Cancer Registry of Norway. Antibodies were analyzed by recently developed multiplex serology based on recombinantly expressed fusions of glutathione-S transferase with viral proteins as antigens combined with fluorescent bead technology. BKV and JCV specific antibodies crossreactive with SV40 were preabsorbed with the respective VP1 proteins. Sera showing SV40 reactivity after preabsorption with BKV and JCV VP1 were further analyzed in SV40 neutralization assays. SV40 DNA was analyzed by SV40 specific polymerase chain reactions. The odds ratio for being a case when tested positive for SV40 VP1 in the antibody capture assay was 1.5 (95% CI 0.6-3.7) and 2.0 (95% CI 0.6-7.0) when only strongly reactive sera where counted as positive. Although some sera could neutralize SV40, preabsorption with BKV and JCV VP1 showed for all such sera that this neutralizing activity was due to cross-reacting antibodies and did not represent truly SV40-specific antibodies. No viral DNA was found in the sera. No significant association between SV40 antibody response in prediagnostic sera and risk of mesothelioma was seen. ' 2007 Wiley-Liss, Inc.Key words: polio vaccination; viral infection; simian virus 40; malignant mesothelioma The rhesus monkey virus Simian Virus 40 (SV40), introduced inadvertently to human populations through contaminated polio vaccine during the years 1956-1963, has repeatedly been shown to induce tumors in animal models and to transform human cells in culture (reviewed in Refs. 1,2). Many types of tumors have been observed, including mesothelioma, ependymoma, osteosarcoma and non-Hodgkin lymphoma, apparently partly dependent on the route of infection. 2 The strong and consistent relation between experimental SV40 infection and cancer development in rodents has motivated the investigation of its carcinogenic potential in humans. SV40 DNA sequences have repeatedly been reported in cases of human cancers of essentially the same types as has been seen in rodents. [3][4][5][6][7] In a meta-analysis including 528 mesothelioma cases and 468 controls from 15 studies, the combined OR for the presence of SV40 DNA sequences in mesothelioma tumor tissue was 17 (95% CI 10-28). 8 SV40 early region sequences have also been detected in human peripheral blood cells, and in preparations...

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Section: Discussionsupporting

confidence: 70%

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples

Kjærheim

Røe

Waterboer

et al. 2007

Intl Journal of Cancer

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“…Contrasting reports have appeared in the literature on the presence of SV40 footprints in humans and its association with human tumors (20)(21)(22). SV40 antibody detection had been attempted in several studies using serologic methods with SV40 virus-like particles (VLPs), but because of high protein homology among the three main polyomaviruses SV40, BKV, and JCV, the results were always affected by some cross-reactivity (23)(24)(25)(26)(27)(28)(29)(30).…”

mentioning

confidence: 99%

High prevalence of serum antibodies reacting with simian virus 40 capsid protein mimotopes in patients affected by malignant pleural mesothelioma

Mazzoni¹,

Corallini

Cristaudo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Human malignant pleural mesothelioma (MPM) is considered a rare tumor, but recent estimations indicate that one-quarter million people will die of this neoplasm in Europe in the next three decades. The mineral asbestos is considered the main causative agent of this neoplasm. MPM is largely unresponsive to conventional chemotherapy/radiotherapy. In addition to asbestos exposure, genetic predisposition to asbestos carcinogenesis and to simian virus (SV) 40 infection has also been suggested. SV40 is a DNA tumor virus found in some studies to be associated at high prevalence with MPM. SV40 sequences have also been detected, although at a lower prevalence than in MPM, in blood specimens from healthy donors. However, some studies have failed to reveal SV40 footprints in MPM and its association with this neoplasm. These conflicting results indicate the need for further investigations with new approaches. We report on the presence of antibodies in serum samples from patients affected by MPM that specifically react with two different SV40 mimotopes. The two SV40 peptides used in indirect ELISAs correspond to viral capsid proteins. ELISA with the two SV40 mimotopes gave overlapping results. Our data indicate that in serum samples from MPM-affected patients (n = 97), the prevalence of antibodies against SV40 viral capsid protein antigens is significantly higher (26%, P = 0.043) than in the control group (15%) represented by healthy subjects (n = 168) with the same median age (66 y) and sex. Our results suggest that SV40 is associated with a subset of MPM and circulates in humans.antibody | neoplasia

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Anti‐JC virus antibodies: Implications for PML Risk Stratification

Gorelik

Lerner

Bixler

et al. 2010

Annals of Neurology

417

360

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This 2-step assay provides a means to classify MS patients as having detectable or not detectable levels of anti-JCV antibodies. The finding that all 17 of the pre-PML samples that were available tested seropositive, and none tested seronegative, warrants further research on the clinical utility of the anti-JCV antibody assay as a potential tool for stratifying MS patients for higher or lower risk of developing PML.

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Lack of Serologic Evidence for Prevalent Simian Virus 40 Infection in Humans

Abstract: These data indicate that some individuals have BKV and/or JCV antibodies that cross-react with SV40, but they do not provide support for SV40 being a prevalent human pathogen.

Cited by 107 publications

References 26 publications

Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples

Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples

High prevalence of serum antibodies reacting with simian virus 40 capsid protein mimotopes in patients affected by malignant pleural mesothelioma

Anti‐JC virus antibodies: Implications for PML Risk Stratification

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