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

International Journal of Cancer. Volume 120, Issue 11, Pages 2459 – 2465 [Link]

Kristina Kjærheim 1 *†, Oluf Dimitri Røe 2 3, Tim Waterboer 4, Peter Sehr 4, Raeda Rizk 4, Hong Yan Dai 5, Helmut Sandeck 5, Erik Larsson 6, Aage Andersen 1, Paolo Boffetta 7, Michael Pawlita 4

1The Cancer Registry of Norway, Oslo, Norway
2Department of Oncology, St. Olavs University Hospital, Trondheim, Norway
3Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
4Research Program Infection and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
5Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway
6Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
7International Agency for Research on Cancer, Lyon, France

email: Kristina Kjærheim (kk@kreftregisteret.no)

*Correspondence to Kristina Kjærheim, The Cancer Registry of Norway, Oslo, Norway

Fax: +47-22-45-13-70.


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 1956-1963, 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 cross- reactive 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.

Keywords: polio vaccination, viral infection, simian virus 40, malignant mesothelioma