Human Exposure to Sv40: Review and Comment12

Shah, Keerti V.; Nathanson, Neal

doi:10.1093/oxfordjournals.aje.a112197

Cited by 314 publications

(194 citation statements)

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“…However, extensive epidemiologic studies on polio vaccine recipients have not shown any significant adverse effect of live wild-type SV40 in humans. 32,33 (4) In addition, as shown in the present work, the administered SV40 virus particle itself elicits no detectable neutralizing antibody response by itself. Animals in which the virus replicates may produce antibodies against these proteins.…”

Section: Discussionsupporting

confidence: 51%

Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent

1998

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We have described a novel gene transfer system, in which subcutaneously into mice every 4 weeks. These mice were replication-incompetent, T antigen-deleted simian virus-40 bled every 2 weeks and their sera assayed for antibody (SV40) is used as the transduction vehicle. We report here activity against HBsAg and SV40. Production of anti-HBs successful immunization using such an SV40-derived viral was measured by ELISA and confirmed by Western blot vector. Hepatitis B surface antigen (HBsAg) cDNA was analysis, both of which demonstrated significant levels of cloned downstream of two tandem SV40 early promoters anti-HBs after the second injection. We also tested proto yield a T antigen-deficient SV40 derivative, SV(HBS).duction of anti-SV40 antibodies by the ability of sera to Cultured TC7 cells were exposed to SV(HBS), and neutralize SV(HBS) infectivity. We found no evidence of expression of HBsAg was detected 24 h later by Northern neutralization of SV(HBS) infectivity even after eight inocublot and RT-PCR analysis. Immunochemistry and Western lations. Thus, replication-incompetent SV40 is itself not a blot analysis were also performed 24 h after infection to strong antigen. Our data suggest that SV40-based transdetect expression of HBsAg. Once it was ascertained that duction systems may be a useful vehicle for immunization we could express HBsAg in this way, we used SV(HBS) to and for other gene transfer applications when a need for elicit anti-HBs. SV(HBS) was injected intraperitoneally or multiple inoculations is anticipated.

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Section: Discussionsupporting

confidence: 51%

Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent

1998

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“…All of the patients were born in 1965 or later (Table I), after the use of SV40-contaminated virus vaccines was discontinued (Shah and Nathanson, 1976). The finding of SV40 DNA in various types of human tumors at significant frequencies suggests that the virus is present in the human population.…”

Section: Reduced Effıciency Of Viral Detection Using Paraffın-embeddementioning

confidence: 99%

“…Subsequently, it was shown that the virus could transform and immortalize human and mouse cells grown in tissue culture. As millions of people had been exposed to SV40 in contaminated virus vaccines (for reviews, see Geissler, 1990;Shah and Nathanson, 1976), there was concern that the virus might be pathogenic in humans; SV40 was studied intensively and became an outstanding model for experimental studies of viral oncogenesis.There is mounting evidence that SV40-like sequences are associated with specific types of human tumors. In the older literature, there were sporadic reports of the detection of SV40 DNA in human tumors (reviewed in Geissler, 1990).…”

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confidence: 99%

SV40 DNA in human osteosarcomas shows sequence variation among T‐antigen genes

et al. 1997

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Authentic simian virus 40 (SV40) has been detected in association with human choroid plexus and ependymoma tumors, and SV40-like DNA sequences have been found in some human osteosarcomas. We report here an analysis of human osteosarcoma samples for the presence of SV40 DNA using PCR and primers directed at 4 distinct sites of the SV40 genome, coupled with sequence analysis. Authentic SV40 DNA sequences were detected in 5 of 10 osteosarcoma tumor samples. The SV40 regulatory region in each case was identical and of archetypal length (non-duplicated enhancer), as is usually found in natural isolates of SV40 from monkeys and in human brain tumors. A section of the gene that encodes a viral late gene product (VP1) was detected in 5 of 10 tumors and had an exact match with the known sequence of SV40. Two separated segments of the large T-antigen (T-ag) gene were found in the same 5 tumors. Analysis of the DNA sequences encoding the T-ag carboxy terminus revealed sequence variation among the tumors, as observed previously in viral DNA associated with human brain tumors. There does not appear to be a preferential association of a T-ag variable domain sequence with a given tumor type. No sequences from the regulatory region of human polyomaviruses JCV and BKV were detected in the bone tumors. We also noted less efficient recovery of SV40 DNA from tumor samples fixed in paraffin as compared to frozen tumors. Our results confirm the presence of SV40 DNA in human bone tumors and, based on the sequence variation observed for the carboxy terminus of the T-ag gene, suggest that there is not a specific SV40 strain associated with human osteosarcomas. Int. J. Cancer 72:791-800, 1997.1997 Wiley-Liss, Inc.Simian virus 40 (SV40) is a small virus containing closed circular double-stranded DNA with limited genetic content (Butel, 1994; Cole, 1996). It was discovered as a contaminant of poliovaccines propagated in rhesus monkey kidney cells. SV40 is endemic in rhesus monkeys, the natural hosts for the virus, where it usually produces no recognizable pathology. Shortly after its discovery, SV40 was demonstrated to be oncogenic in newborn hamsters, in the African rodent Rattus natalensis and in certain inbred strains of mice. Subsequently, it was shown that the virus could transform and immortalize human and mouse cells grown in tissue culture. As millions of people had been exposed to SV40 in contaminated virus vaccines (for reviews, see Geissler, 1990;Shah and Nathanson, 1976), there was concern that the virus might be pathogenic in humans; SV40 was studied intensively and became an outstanding model for experimental studies of viral oncogenesis.There is mounting evidence that SV40-like sequences are associated with specific types of human tumors. In the older literature, there were sporadic reports of the detection of SV40 DNA in human tumors (reviewed in Geissler, 1990). More recent studies have used sensitive PCR technology and have detected the presence and expression of SV40-related sequences in pediatric ependymoma and choroid ...

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“…40 SV40 is a monkey virus, which was believed to be transmitted to humans only under exceptional situations in natural infection. 42 SV40 contaminated vaccines, 42,43 in particular, antipolio vaccines, were administered to millions of humans worldwide between 1955 and 1963. 44,45 However, the presence of this viral agent in humans, before the introduction of SV40-contaminated vaccines, cannot be discarded.…”

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confidence: 99%

Different simian virus 40 genomic regions and sequences homologous with SV40 large T antigen in DNA of human brain and bone tumors and of leukocytes from blood donors

Martini

Lazzarin

Iaccheri

et al. 2002

Cancer

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BACKGROUNDMany studies found only a small fragment of the large T‐antigen coding sequences in human tumors, raising doubts on authenticity of SV40 sequences detected in these samples.METHODSFive different regions of SV40 DNA were investigated in 106 fresh human tumor biopsies (25 brain, 69 bone, 12 Wilms' tumors), 71 tumor‐derived cell cultures (38 from brain and 33 from bone tumors) and normal tissues (5 fresh bone biopsies and 38 buffy coats) by polymerase chain reaction (PCR) techniques and filter hybridization with specific oligoprobes. Expression of SV40 Tag sequences was analyzed in human tumor specimens by RT‐PCR.RESULTSSV40 large T‐antigen sequences were detected at high prevalence, in human biopsies of primary brain (37–44%) and bone (21–37%) tumors, in cell cultures derived from brain (30–54%) and bone (53–80%) tumors. SV40 Tag sequences were detected in 29% of buffy coats of blood donors. However, only four brain tumor cell lines showed all the five regions of the SV40 genome investigated. Expression of SV40 Tag sequences was found in 11 of 27 (41%) human tumor samples. DNA sequence analysis indicated that the PCR‐amplified products belong to the SV40 wild type. Polymerase chain reaction products of Tag middle portion from 20 of 78 (26%) samples showed a 97% homology with telomeric sequences of human chromosomes 10 and 11.CONCLUSIONSAuthentic SV40 sequences were detected in human samples. The expression of SV40 Tag sequences indicates that SV40 could play a role, as a cofactor, in the onset/progression of specific human cancers. The inability to detect some regions of the virus genome may suggest that those regions are not required for tumor persistence or growth and have been lost or, alternatively, may be the result of assay conditions that were unable to PCR‐amplify those regions in the tumors. Cancer 2002;94:1037–48. © 2002 American Cancer Society.DOI 10.1002/cncr.10272

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Human Exposure to Sv40: Review and Comment12

Cited by 314 publications

References 0 publications

Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent

Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent

SV40 DNA in human osteosarcomas shows sequence variation among T‐antigen genes

Different simian virus 40 genomic regions and sequences homologous with SV40 large T antigen in DNA of human brain and bone tumors and of leukocytes from blood donors

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