Identification of a Variable Region at the Carboxy Terminus of SV40 Large T-Antigen

Stewart, A. Renee; Lednicky, John A.; Benzick, Uma S.; Tevethia, Mary J.; Butel, Janet S.

doi:10.1006/viro.1996.0386

Cited by 37 publications

(26 citation statements)

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“…It is noteworthy, however, that the sequence of the T-ag-C variable region differed among the three SV40 isolates (strains 776, SV40-B and VA45-54 ; Fig. 3 b), confirming our previous observations (Stewart et al, 1996) that the carboxy terminus of T-ag contains a variable domain. Four randomly chosen clones of each genome type of pSV40-VA45-54 were linearized with EcoRI and transfected into CV-1 cells.…”

Section: Genetic Analysis Of Sv40 Strain Va45-54supporting

confidence: 89%

“…3 b) and with the sequence determined previously for an independent lineage of SV40-VA45-54 (Fig. 1 b ; Stewart et al, 1996), indicating that the T-ag-C sequence of strain SV40-VA45-54 had not changed over many years. It is noteworthy, however, that the sequence of the T-ag-C variable region differed among the three SV40 isolates (strains 776, SV40-B and VA45-54 ; Fig.…”

Section: Genetic Analysis Of Sv40 Strain Va45-54supporting

confidence: 79%

“…(b) Carboxy-terminal T-ag sequences of cloned viruses derived from lowpassage source stocks of strains SV40-B and SV40-VA45-54. With each virus strain, the T-ag sequence was the same for variants having archetypal (type 1) or duplicated (type 2) regulatory regions (from this study) and identical to the sequence determined earlier using virus with different passage histories Stewart et al, 1996). The T-ag-C sequence is also shown for prototype SV40 strain 776.…”

Section: Genetic Analysis Of Sv40 Baylor Strainmentioning

confidence: 78%

“…Sequence comparison of the entire early region of several isolates of SV40 obtained from monkeys and humans and recovered over a span of 35 years recently confirmed the existence of a short variable domain at the carboxy terminus of T-ag (T-ag-C ; encompassing amino acids 622-708) (Stewart et al, 1996). Except for the short variable region, the amino acid sequence of T-ag was absolutely conserved among the virus isolates.…”

Section: Introductionmentioning

confidence: 91%

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Tissue culture adaptation of natural isolates of simian virus 40: changes occur in viral regulatory region but not in carboxy-terminal domain of large T-antigen.

Lednicky

Butel

1997

Journal of General Virology

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The regulatory region of natural isolates of simian virus 40 (SV40) is different from that of laboratoryadapted strains of the virus. The latter have a nucleotide sequence duplication within the enhancer region which varies slightly with each strain, whereas the duplication is lacking in fresh isolates of SV40, which contain an ' archetypal ' regulatory region. Many isolates also display nucleotide differences in the DNA encoding the carboxy terminus of large tumour antigen (T-ag). To determine whether genetic changes in these two regions of the SV40 genome were detectable during laboratory adaptation and long-term passage, low-passage virus stocks of two laboratory strains which had detailed passage histories spanning more than 25 years (Baylor strain and VA45-54) were analysed using PCR, cloning and sequencing assays. Both

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Section: Genetic Analysis Of Sv40 Strain Va45-54supporting

confidence: 89%

Section: Genetic Analysis Of Sv40 Strain Va45-54supporting

confidence: 79%

Section: Genetic Analysis Of Sv40 Baylor Strainmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 91%

See 2 more Smart Citations

Tissue culture adaptation of natural isolates of simian virus 40: changes occur in viral regulatory region but not in carboxy-terminal domain of large T-antigen.

Lednicky

Butel

1997

Journal of General Virology

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“…Sequences from SV40 were also detected in normal tissue from six osteosarcoma patients (Carbone et al, 1996). Structural analysis of the SV40 origin of replication and the C-terminal Tantigen regions suggests that SV40 found in tumors are distinct non-laboratory strains (Stewart et al, 1996;Lednicky et al, 1995). Overall, these observations suggest that SV40 might have a role in the pathogenesis of human cancer, or at least have a tropism to certain tumors.…”

Section: Introductionmentioning

confidence: 85%

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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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.

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Identification of a Variable Region at the Carboxy Terminus of SV40 Large T-Antigen

Cited by 37 publications

References 0 publications

Tissue culture adaptation of natural isolates of simian virus 40: changes occur in viral regulatory region but not in carboxy-terminal domain of large T-antigen.

Tissue culture adaptation of natural isolates of simian virus 40: changes occur in viral regulatory region but not in carboxy-terminal domain of large T-antigen.

Integration of SV40 in human osteosarcoma DNA

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

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