No evidence of HIV and SIV sequences in two separate lots of polio vaccines used in the first U.S. polio vaccine campaign.

We obtained sealed vials of two different polio vaccine lots, expiration date 1955, which were used in the first U.S. polio vaccine campaign. These early lots were pulled from the market because they contained live infectious poliovirus which caused polio in some of the vaccines. Theoretically, these vaccines could have contained other infectious retroviruses, including HIV. No viral sequences were detected using RT-PCR analyses with primers capable of amplifying chimpanzee SIV and HIV-1-related viruses nor with primers for macaque SIV, sooty mangabey SIV, and HIV-2-related viruses. Poliovirus sequences were readily amplified by RT-PCR, suggesting that the technique used would have detected SIV or HIV sequences, if present.

Simian virus 40 is present in most United States human mesotheliomas, but it is rarely present in non-Hodgkin's lymphoma.

Simian virus 40 (SV40) causes mesotheliomas, osteosarcomas, ependymomas, choroid plexus tumors, and lymphomas in hamsters. In humans, SV40 has been detected in tumors of the first four types. Using the polymerase chain reaction (PCR), we tested 29 non-Hodgkin's lymphomas (intermediate and high-grade), 25 posttransplant lymphoproliferative disorders, and 5 AIDS lymphomas for SV40 DNA. PCR analysis revealed that 3 of 29 lymphomas, 6 of 25 posttransplant lymphoproliferative disorders, and 2 of 5 AIDS lymphomas contained SV40 sequences corresponding to the retinoblastoma (RB)-pocket binding domain of SV40 tumor antigen (Tag). However, among positive samples, only one posttransplant lymphoproliferative disorder and one AIDS lymphoma contained the SV40 regulatory region, which suggest a higher viral load in these patients. In parallel experiments, 8 of 12 mesotheliomas tested positive for SV40 for both the RB-pocket binding domain of Tag and the SV40 regulatory region. These data confirm the presence of SV40 in most United States mesotheliomas and indicate that in human non-Hodgkin's lymphomas, the prevalence of SV40 is low.

The biological activities of simian virus 40 large-T antigen and its possible oncogenic effects in humans.

Simian virus 40 (SV40) is an oncogenic virus which induces tumors in hamsters and transforms human cells in tissue culture. Between 1955 and 1963, polio vaccines and adenovaccines were contaminated with SV40; therefore, millions of people were exposed to this oncogenic virus. The SV40 proteins responsible for in vivo oncogenesis and in vitro cell transformation are encoded by the early region of the virus. These proteins are called T (tumor) antigens (Tags), because animals with tumors induced by SV40 have antibodies against these viral proteins. Recently, we and other research laboratories have found SV40 in specific types of human tumors: mesothelioma, ependymoma and choroid plexus tumors, osteosarcoma and sarcoma. The same tumor types will develop in hamsters which have been injected systemically with SV40. SV40 causes cell transformation in tissue culture and tumors in animals, because SV40 Tag binds and inactivates the cellular tumor suppressor gene products, Rb and p53. We found that SV40 Tag binds p53 and Rb in human mesotheliomas, possibly contributing to the malignant phenotype.

The detection of simian virus 40 in human tumors by polymerase chain reaction.

Simian virus (SV) 40 is a deoxyribonucleic acid (DNA) virus that induces mesotheliomas, ependymomas, bone tumors, and lymphomas in hamsters. In recent years SV40 sequences have been detected in approximately 60% of mesotheliomas and ependymomas, in 33% of bone tumors and sarcomas, and in 13% of lymphomas. Because the amount of human specimens available for molecular studies is usually minimal, the method most commonly used to demonstrate SV40 in human specimens is the polymerase chain reaction (PCR). PCR is a highly sensitive and useful technique. In the PCR reaction, different sets of primers are used for targeting different regions of DNA. The regions of the SV40 genome targeted by PCR include the large T-antigen, the small t-antigen, the origin of replication, and viral protein-1 capsid protein. The use of these different sets of primers to test human tumor specimens for SV40 produce a different percentage of positive results. This is because these experiments revealed that some primers are more specific than others which may also detect sequences belonging to other DNA papovaviruses. Therefore, the combined use of different sets of primers is recommended when it is important to distinguish SV40 from other related papovaviruses such as BK and JC, which can also be occasionally present in human cells. Furthermore, these experiments demonstrated that polymerase chain reaction analyses for simian virus 40 can be performed better and easier when using deoxyribonucleic acid extracted from fresh and/or frozen tissue. Deoxyribonucleic acid from paraffin embedded specimens should not be used routinely for simian virus 40 testing because of the high risk of obtaining false negative results. However, these paraffin derived deoxyribonucleic acids can be used reliably in molecular laboratories specialized in these type of analyses. This paper describes the methods that we have developed to test simian virus 40 in human specimens.