Transformation of Cultures of Human Tissue Infected with Simian Virus SV<sub>40</sub>

Koprowski, Hilary; Pontén, Jan; Jensen, Fred C.; Ravdin, Robert G.; Moorhead, Paul S.; Saksela, Eero

doi:10.1002/jcp.1030590308

Cited by 236 publications

(58 citation statements)

References 7 publications

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“…In some cell systems, small t antigen has been reported to increase the e ciency of immortalization and transformation, although t is neither clastogenic nor aneuploidogenic (Bikel et al, 1987;Choi et al, 1988). The high frequency of cells containing dicentric chromosomes (15 of 100 cells) within 10 days after T expression is consistent with previous karyotype analyses of human cells infected with SV40 virus (Koprowski et al, 1962;Wolman et al, 1964). T also caused four chromatid exchange events, extremely rare events, in 100 normal diploid human cells.…”

Section: Discussionsupporting

confidence: 82%

“…Earlier studies have established the rapid appearance of karyotype defects following infection of rodent and human cells with SV40 virus (Koprowski et al, 1962;Wolman et al, 1964), and here we observe that large T alone induces aberrations very shortly after its expression. Other SV40 products, such as small t antigen, are not necessary for the induction of early defects.…”

Section: Discussionsupporting

confidence: 77%

“…Shown are the 5' LTR, 3' LTR, SV40 early promoter (SV), Tn5 neomycin phosphotransferase gene (neo), origin of replication, and ampicillin resistance gene (Ap) from pLXSN. The SV40 T coding sequence is from pRSVEdl884 reporting high frequencies of dicentric chromosomes in human cells infected with SV40 virus (Koprowski et al, 1962;Wolman et al, 1964). These observations demonstrate that T antigen alone rapidly causes numerical and structural chromosome aberrations after expression in normal human cells, that this activity requires no assistance from small t or any other SV40 molecule, and that the aberrations produced are similar to those seen with wild type SV40 virus.…”

Section: T Rapidly Induces Chromosome Aberrationsmentioning

confidence: 99%

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Disregulation of mitotic checkpoints and regulatory proteins following acute expression of SV40 large T antigen in diploid human cells

Chang

Ray

et al. 1997

Oncogene

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SV40 large T antigen (T) inactivates the tumor suppressor proteins p53 and pRb, and can induce cells to enter DNA replication at inappropriate times. We show here that T also compromises three cell cycle checkpoints that regulate the entry into and exit from mitosis. Human diploid ®broblasts infected with a retrovirus expressing T displayed an attenuated radiation-induced mitotic delay, were more susceptible to chemical-induced uncoupling of mitosis from the completion of DNA replication, and were more likely to exit mitosis and rereplicate their DNA when mitotic spindle assembly was inhibited. Consistent with altered mitotic checkpoint control, cells expressing T displayed elevated protein levels and/or associated activities of the mitotic regulatory proteins cyclin A, cyclin B, Cdc25C and p34 cdc2 . These changes in mitotic control were evident within 5 ± 10 population doublings after retroviral infection, indicating a direct e ect of T expression. Cells acutely infected with the T-expressing retrovirus su ered numerical and structural chromosome aberrations, including increases in aneuploidy, dicentric chromosomes, chromatid exchanges and chromosome breaks and gaps. These ®ndings indicate that T rapidly disrupts mitotic checkpoints that help maintain genomic stability, and suggest mechanisms by which T induces chromosome aberrations and promotes the immortalization and neoplastic transformation of human cells.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 77%

Section: T Rapidly Induces Chromosome Aberrationsmentioning

confidence: 99%

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Disregulation of mitotic checkpoints and regulatory proteins following acute expression of SV40 large T antigen in diploid human cells

Chang

Ray

et al. 1997

Oncogene

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“…Tissue speci®c expression of T-antigen in transgenic mice can cause cancers in target organs or yield cells which can be grown in culture (Fox et al, 1989;Sepulveda et al 1989). Polyomavirus infection leads to transformation or lysis of cell lines, depending on species and cell type (Shay et al, 1993;Koprowski et al, 1964). The early region of polyomaviruses, encoding large Tantigen, su ces for transforming cells in culture (Fanning and Knippers, 1992).…”

Section: Introductionmentioning

confidence: 99%

Integration of SV40 in human osteosarcoma DNA

1998

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Simian virus 40 (SV40) has been demonstrated in several types of tumors, including osteosarcoma, by polymerase chain reaction (PCR). We detected SV40 sequences by PCR, followed by hybridization, in nine of 35 osteosarcoma tumors and one of 11 osteosarcoma explants. PCR can detect fewer than one virus per cell but gives little detail of the gross structure and abundance of the virus. Analysis by Southern blotting of total DNA from ten osteosarcomas, positive for SV40 by PCR, found viral integration in half of these. Analysis showed integration of one to four copies per cell of rearranged SV40. No SV40 was detectable on blots of the remaining ®ve SV40 + osteosarcomas, perhaps because of the lesser sensitivity of direct hybridization. Inactivation of the p53 and Rb tumor suppressors is a key activity of SV40 T-antigen. Unexpectedly, correlation of these ®ndings with our prior studies indicated that ®ve of ten osteosarcomas positive for SV40 DNA had mutations of p53, and two had deleted Rb. Apparently clonal integration with pre-existing alteration of a tumor suppressor gene, suggests that SV40 may play a role in the ®nal conversion to malignant osteosarcoma.

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“…Nevertheless, mouse cells have been transformed by polyoma virus (Dulbecco & Vogt, 1960) and monkey and human cells by simian virus 40 (SV40) (Fernandes & Moorhead, 1965;Carp & Gilden, 1966;Koprowski et al, 1962;Shein & Enders, 1962). BK virus (BKV), a human papovavirus isolated by Gardner et al (1971), is oncogenic for hamsters and mice and transforms hamster, mouse, rat, rabbit and monkey cells in culture (for reviews see Howley, 1980;Padgett, 1980).…”

Section: Introductionmentioning

confidence: 99%

Transformation of Human Embryonic Fibroblasts by BK Virus, BK Virus DNA and a Subgenomic BK Virus DNA Fragment

Grossi

Caputo

Meneguzzi

et al. 1982

Journal of General Virology

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SUMMARYHuman embryonic fibroblasts (HEF) have been transformed by BK virus (BKV) DNA and by u.v.-inactivated or live BKV alone or in association with methylcholanthrene (MTC). The transformed cells produced BKV large T and small t antigens as well as the cellular 53 kdal protein, detected by immunofluorescence and immunoprecipitation. After an initial phase of lysis and virus shedding, virus or its coat protein antigen could not be detected in transformed cells. All human transformed cell lines could be superinfected by BKV or BKV DNA, but their susceptibility to superinfection was 20-to 500-fold lower than normal HEF. BKV could be rescued by fusion of transformed cells with normal HEF or Veto cells and by transfection of normal HEF with total DNA and DNA extracted from the Hirt supernatant of transformed cells. Blot hybridization analysis of DNA from transformed cells showed a considerable amount of free BKV DNA in monomeric and polymeric forms. Integrated BKV DNA was absent in most cell lines but present in only small amounts in BKV-transformed cells treated with MTC. Analysis of free BKV DNA with various restriction endonucleases and by blot hybridization showed that monomeric forms were complete BKV genomes, whereas polymers contained both complete and defective or rearranged BKV DNA. Transformation of HEF was also obtained with a 3.7 kilobase (kb) fragment of the BKV genome, produced by sequential digestion of BKV with the restriction endonucleases HhaI and EcoRI. This fragment extends clockwise on the virus genome from 0 to 72-2 map units and contains the entire early region. Blot hybridization analysis of cells transformed by the HhaI/EcoRI 3.7 kb fragment showed two separate integrations of BKV sequences without free virus DNA.

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Transformation of Cultures of Human Tissue Infected with Simian Virus SV₄₀

Cited by 236 publications

References 7 publications

Disregulation of mitotic checkpoints and regulatory proteins following acute expression of SV40 large T antigen in diploid human cells

Disregulation of mitotic checkpoints and regulatory proteins following acute expression of SV40 large T antigen in diploid human cells

Integration of SV40 in human osteosarcoma DNA

Transformation of Human Embryonic Fibroblasts by BK Virus, BK Virus DNA and a Subgenomic BK Virus DNA Fragment

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Transformation of Cultures of Human Tissue Infected with Simian Virus SV40

Cited by 236 publications

References 7 publications

Disregulation of mitotic checkpoints and regulatory proteins following acute expression of SV40 large T antigen in diploid human cells

Disregulation of mitotic checkpoints and regulatory proteins following acute expression of SV40 large T antigen in diploid human cells

Integration of SV40 in human osteosarcoma DNA

Transformation of Human Embryonic Fibroblasts by BK Virus, BK Virus DNA and a Subgenomic BK Virus DNA Fragment

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Transformation of Cultures of Human Tissue Infected with Simian Virus SV₄₀