Simian virus 40, poliovaccines and human tumors: a review of recent developments

Abstract

Recently, wild-type SV40 and/or DNA sequences indistinguishable from SV40 have been detected in speci®c types of human tumors: ependymoma and choroid plexus tumors, mesothelioma, osteosarcoma and sarcoma. The same tumor types will develop in hamsters after injection with SV40. These ®ndings are interesting in themselves for they could shed light on the pathogenesis of these tumors. These ®ndings also have public health implications. SV40 was found to have contaminated the poliovaccines and the adenovaccines from 1955 until 1963, therefore resulting in the inadvertent injection of millions of people with this tumor virus. Moreover, our society pays a high cost for asbestos causality, a carcinogen associated with the development of mesothelioma. In addition to asbestos, the potential impact of ®nding another possible cause for mesothelioma (i.e., SV40), as well as the possible pathogenic role of the contaminated poliovaccines, has generated considerable public interest and concern. To discuss these recent ®ndings, the NIH (National Institutes of Health) and the FDA (Food and Drug Administration), organized an International Conference at the NIH, Bethesda, MD, January 27 ± 28, 1997. The association of SV40 with human mesothelioma was also discussed in a special session at the IV International Mesothelioma Conference that was held at the University of Pennsylvania, Philadelphia, PA, May 13 ± 16, 1997. The purpose of this review is to summarize data, from the discovery of the contaminated poliovaccines, to the most recent ®ndings presented at the meetings in Bethesda and Philadelphia, to discuss technical and other problems associated with this research, and the potential for using these ®ndings to develop new diagnostic and therapeutic approaches for SV40-associated malignancies.

Integration of SV40 in human osteosarcoma DNA

“…Sequencing of ampli®ed fragments was used as ultimate proof of identity. These primers have been widely used to screen for SV40 and BKV in human tumors (Carbone et al, 1997). Fragments consistent with SV40 were found in nine of 35 of osteosarcoma tumors (26%) and one of 11 osteosarcoma explants.…”

“…Southern blots detected BKV DNA in 30% of cadaver kidneys from patients expiring from non-cancer causes, and, likewise, BKV DNA was detected in various tissues by PCR (Chesters et al, 1983;DeMattei et al, 1995). The signi®cance of SV40 in human tissues continues to be elucidated (Carbone et al, 1997). Cultivation of SV40 from a melanoma is an early example suggesting a link might exist between SV40 infection and cancer (Soriano et al, 1974).…”

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

“…A report by the Institute of Medicine (IOM) concludes that the evidence is insufficient to prove or disprove the theory that exposure to SV40-contaminated poliovirus vaccine resulted in cancer in humans (http://www.iom.edu/iom/iomhome.nsf/pages/ Sv40+Report?OpenDocument), so the issue remains open (Carbone et al, 1997;Klein et al, 2002;BarbantiBrodano et al, 2004;Engels, 2005). Conversely, although the presence of SV40 in humans can still be considered just incidental, JCV is estimated to infect up to 90% of the humans.…”

Lack of association of cytomegalovirus with human brain tumors

“…Simian virus 40, a contaminant of polio vaccines utilized between 1955 and 1963, [8][9][10] in particular has been implicated as a causative agent in the development of neurologic malignancies, as viral sequences have been detected in brain tumors at an overall frequency of approximately 35%. [9][10][11][12] However, epidemiological data have not supported a clear relationship between virus-contaminated vaccinations and an increased risk for brain tumors. 8,10,13 Human cytomegalovirus (CMV) possesses many oncogenic properties and has been linked to several different human malignancies.…”

“…[9][10][11][12] However, epidemiological data have not supported a clear relationship between virus-contaminated vaccinations and an increased risk for brain tumors. 8,10,13 Human cytomegalovirus (CMV) possesses many oncogenic properties and has been linked to several different human malignancies. 14-17 CMV has not been well investigated in the context of malignant gliomas, but a recent report has documented the presence of CMV in a number of these tumors.…”