Lack of serological evidence for an association between simian virus 40 and lymphoma

Abstract

Recent studies have implicated simian virus 40 (SV40) in non-Hodgkin's lymphomas based on detection of SV40 DNA sequences. We employed a virus-like-particle (VLP)-based enzyme immunoassay for antibodies to SV40 to test sera from 520 lymphoma cases and 587 controls in Spain. The SV40 seroprevalence was 9.5% in controls and 5.9% in cases. Antibody levels of the positive sera were low. There was no association of SV40 seropositivity with any subtype of lymphoma. VLPs of the human BK virus substantially inhibited the SV40 reactivity of human sera. There was no serological evidence of widespread SV40 infection and no association of SV40 seropositivity with human lymphomas in Spain. © 2003 Wiley-Liss, Inc. Recent reports of the detection of simian virus 40 (SV40) DNA sequences in non-Hodgkin's lymphomas 1,2 add to a growing list of human cancers that may be associated with SV40 DNA positivity. 3 SV40 is a natural infection of Asiatic macaques to which millions of people were inadvertently exposed through contaminated poliovirus vaccines administered between 1955 and 1963. These vaccines were used in Spain but not applied universally. 4 Furthermore, the detection of SV40 in cancers in persons born after 1963 suggests that the virus may have established itself in human populations and is transmitted by person-to-person spread. Previous reports have largely relied on detection of viral DNA as evidence of SV40 infection. If SV40 circulates in human populations and is implicated in lymphomas, one might expect to detect serum antibodies to SV40 in lymphoma cases. We have employed a newly developed enzyme immunoassay (EIA) for SV40 antibodies 5 in a seroepidemiological study to evaluate the association between SV40 infection and lymphomas.Study subjects were recruited at 4 centers in Spain: Barcelona, Tortosa, Reus and Madrid. Cases were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002. The diagnosis of lymphoma was verified by histology or cytopathology. Cases were categorized according to WHO Classification for Neoplastic Diseases of the Lymphoid Tissues. Controls were hospitalized patients matched to the cases by 5-year age group, gender and study center. Interviews were conducted to collect data on demographic, medical and family history, and environmental exposures. Cases and controls provided a blood sample. Informed consent was obtained from all subjects and the Institutional Review Boards of the participating centers approved the study.Of 703 eligible cases, 520 (74.0%) were included in the seroepidemiological study. Reasons for exclusion were refusal to participate (n ϭ 28), death before the interview (n ϭ 25), absence of blood sample (n ϭ 125) and absence of interview (n ϭ 5). Of 655 eligible controls, 587 (89.6%) were included in the study. Reasons for exclusion were refusal to participate (n ϭ 23) and absence of a blood sample (n ϭ 45).A recombinant baculovirus expressing VP1, the major capsid protein of SV40, was constructed and insect cells were infected with the virus. V...

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

“…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.…”

Polyomavirus SV40 infection and lymphomas in Spain

“…We read with interest the report of De SanJose et al, 1 in which the authors performed a retrospective seroepidemiologic study to determine the presence of polyomavirus SV40 antibodies using an enzyme immunoassay (EIA) in patients with lymphoma in Spain. The authors reported detection rates of 5.9% for SV40 antibodies in patients with lymphoma and 9.5% for controls.…”

“…[2][3][4] These are important findings because SV40 oncogenesis is mediated in large part by T-ag and its effects on tumor-suppressor proteins. [2][3][4] While De SanJose et al 1 investigated an aspect of the relation between SV40 infection and cancer development in humans, 2 important issues need to be considered. First, studies conducted over the last 3 decades have indicated that SV40 infections occur in children and adult populations today, but the prevalence of infections in any particular population is not known, with available data being limited and inconclusive.…”

“…However, as cancer can have many causal factors, geographic variation in the frequency of involvement of polyomavirus SV40 in certain malignancies would not rule out the etiologic importance of the virus where present. 4 The validity of observational studies such as the retrospective analysis by De SanJose et al 1 depends on the accuracy of the existing knowledge of the biologic properties of SV40 and identification of the human population infected with the virus. [2][3][4] Supportive evidence from experimental studies is required to draw causal inferences to human disease.…”

“…2,4 Contaminated polio vaccines reportedly were used in Spain. 1 The actual number of people infected with SV40 through the use of any contaminated polio vaccine is not known. 2,4 In the United States, not all vaccine lots were contaminated with SV40, formalin inactivation reduced the titer of live SV40 in the lots that were contaminated and the frequency of successful infection following inoculation with these vaccine lots is unknown.…”