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

Abstract

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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