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Thorax Nov 1996DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small t antigens (SV40LTAg), suggestive of an aetiopathogenetic link...
BACKGROUND
DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small t antigens (SV40LTAg), suggestive of an aetiopathogenetic link have been identified in fresh frozen tissue of a high proportion of recent cases of pleural mesotheliomas from the United States, Italy and Germany. SV40 is not normally infective in man though it can transform human cells in tissue culture. A large cohort of people in the western world was accidentally parenterally inoculated with live SV40 through contaminated polio vaccines given between 1959 and 1961, and this might be a factor in the current continuing rise in the incidence of mesothelioma in the United States, Britain and Europe. The present study investigated the presence of SV40LTAg DNA in recently diagnosed cases of mesothelioma in Britain and the feasibility of detecting the SV40 DNA in archival tissue for retrospective analysis of cases in the peri-vaccination period.
METHODS
DNA was extracted from fresh frozen and/or rehydrated formalin fixed, paraffin embedded tissue sections from nine recently diagnosed cases of mesothelioma, nine cases of pulmonary adenocarcinoma, and three reactive pleurae, and amplified by the polymerase chain reaction (PCR) using the primer pairs used previously on fresh frozen tissues-namely, the SV primer set directed at the LTAg gene sequence unique to SV40 and the PYV primer set directed at a sequence shared by SV40 and papovavirus strains BK and JC, respectively.
RESULTS
PCR positivity with the SV primer set was restricted to four of the nine cases of mesothelioma. In contrast, six of the nine mesotheliomas, two of the nine adenocarcinomas, and one of the three reactive pleurae showed positivity with the PYV primers. The fresh frozen and corresponding formalin fixed, paraffin embedded tissue results concorded well with each other.
CONCLUSIONS
Our data provide evidence for the association of SV40LTAg primer specific DNA with human pulmonary mesothelioma in the British population.
Topics: Adult; Aged; Antigens, Viral; Cryopreservation; DNA, Viral; Female; Formaldehyde; Humans; Male; Mesothelioma; Middle Aged; Paraffin Embedding; Pleural Neoplasms; Polymerase Chain Reaction; Simian virus 40
PubMed: 8958887
DOI: 10.1136/thx.51.11.1074 -
The EMBO Journal Jan 1992Simian virus 40 (SV40) and polyomavirus (Py) DNA replication require cellular proteins and a virus-encoded early gene product, large T antigen (SVT and PyT,... (Comparative Study)
Comparative Study
Simian virus 40 (SV40) and polyomavirus (Py) DNA replication require cellular proteins and a virus-encoded early gene product, large T antigen (SVT and PyT, respectively). Primate cells contain factors permissive for SV40 replication, whereas murine cells express those factors permissive for Py. We have compared the roles T antigen, cell permissiveness and replication play in transcription of SV40 and Py genes. We show that in their respectively permissive cells, SV40 replication causes a major shift in transcription initiation from the early to the late viral promoter, whereas when Py replicates a comparable shift does not occur. This difference is discussed in relation to differences in the organization of the origin and promoter region between these two papovaviruses. Reporter plasmids were constructed that carried both viral origins, one at the natural position in the promoter being tested and the other at a distal location. With the appropriate TAg, these vectors could be made to replicate in either primate (HeLa) or rodent (3T6) cells. The SV40 early to late shift occurred when replication was driven in HeLa cells, and was not seen on replicating templates in rodent cells. Thus, replication per se does not account for the shift. We show also that, like SVT, PyT is a potent activator of transcription, and that SVT and PyT can activate each other's late promoters independently of DNA replication, but only in cells permissive for DNA replication catalysed by the respective T antigen. Taken together, the data presented here suggest that papovaviruses may utilize permissive factors in transcription control mechanisms.
Topics: Animals; Antigens, Viral, Tumor; Cell Line; DNA Replication; Gene Expression Regulation, Viral; Humans; Mice; Papillomaviridae; Polyomaviridae; Polyomavirus; Promoter Regions, Genetic; Simian virus 40; Transcription, Genetic; Transcriptional Activation
PubMed: 1310931
DOI: 10.1002/j.1460-2075.1992.tb05040.x -
Proceedings of the National Academy of... Jul 1994Synergism between transcriptional activators is a powerful way of potentiating their function. Here we show that the glial POU domain protein Tst-1 (also known as Oct-6...
Synergism between transcriptional activators is a powerful way of potentiating their function. Here we show that the glial POU domain protein Tst-1 (also known as Oct-6 and SCIP) and large tumor antigen (T antigen) synergistically increased transcription from both the early and the late promoters of papovavirus JC in glial cells. Synergism between both proteins did not require T-antigen-mediated DNA replication or direct binding of T antigen to the promoter. The ability of T antigen to functionally cooperate with Tst-1 was contained within its N-terminal region, shown by the fact that small tumor antigen (t antigen) could substitute for T antigen in transfection experiments. In addition to this functional synergism, a direct interaction between Tst-1 and T antigen was observed in vitro. Using deletion mutants of Tst-1 and T antigen, the POU domain of Tst-1 and the N-terminal region of T antigen were found to participate in this interaction. Because of the low levels of Tst-1 present in oligodendrocytes, synergism between Tst-1 and T antigen could be an important factor in establishing the lytic infection of oligodendrocytes by JC virus during the course of the fatal demyelinating disease progressive multifocal leukoencephalopathy.
Topics: Antigens, Polyomavirus Transforming; Base Sequence; Cell Line; DNA Replication; DNA-Binding Proteins; Electrophoresis, Polyacrylamide Gel; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Viral; Glioblastoma; Glutathione Transferase; Humans; Immunoblotting; JC Virus; Luciferases; Molecular Sequence Data; Molecular Weight; Mutagenesis; Octamer Transcription Factor-6; Plasmids; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; Sequence Deletion; Transcription Factors; Transcription, Genetic; Transfection; Tumor Cells, Cultured
PubMed: 8022800
DOI: 10.1073/pnas.91.14.6433 -
Nucleic Acids Research Oct 1979Extensive physical mapping revealed that approximately 90% of the genomes of BKV(prototype, WT) and BKV (MM strain) are identical or closely related. Nucleotide... (Comparative Study)
Comparative Study
Extensive physical mapping revealed that approximately 90% of the genomes of BKV(prototype, WT) and BKV (MM strain) are identical or closely related. Nucleotide sequences of the non-homologous regions and a large portion of the homologous regions have been determined for both genomes. The coding sequence of small t antigen of BKV(MM) is 216 nucleotides shorter than that of BKV(WT), even though no differences in biological function of the t antigen was observed. Both genomes contain three similar sets of 44-61 base-pair repeated sequences. However, the DNA sequence of the tandem repeats is totally different between BKV (human cell as host) and SV40 (monkey cell as host). On the other hand, the region between the N-terminus of the T antigen genes and the origin of replication is dominated by a similar set of palindromic sequences in BKV and SV40 DNA. There is also extensive homology between the regions which code for proteins in BKV and SV40, suggesting a close evolutionary relationship.
Topics: Antigens, Viral; BK Virus; Base Composition; Base Sequence; DNA Restriction Enzymes; DNA, Viral; Genes, Viral; Papillomaviridae; Polyomaviridae; Polyomavirus; Protein Biosynthesis; Simian virus 40; Species Specificity; Transcription, Genetic
PubMed: 228246
DOI: 10.1093/nar/7.3.651 -
Journal of Virology Oct 1978The antigenic relationship between the two murine papovaviruses, K virus and polyoma virus, was examined by serological techniques to determine whether they shared any... (Comparative Study)
Comparative Study
The antigenic relationship between the two murine papovaviruses, K virus and polyoma virus, was examined by serological techniques to determine whether they shared any antigenic components. No cross-reactivity was found associated with the viral (V) antigens by the indirect immunofluorescence, neutralization, or hemagglutination-inhibition tests. The tumor (T) antigens expressed in transformed cells or cells productively infected by either K or polyoma virus did not cross-react by indirect immunofluorescence. An antigenic relationship was detected, however, among the late proteins of K virus, polyoma virus, simian virus 40, and the human papovavirus BKV, when tested with either hyperimmune sera prepared against polyoma virus and simian virus 40 or sera prepared against disrupted virions. The nucleic acids of K and polyoma viruses were compared by agarose gel electrophoresis and restriction endonuclease analysis. No nucleotide sequence homology between the genomes of these two viruses was detectable by DNA-DNA hybridization techniques under stringent conditions. The genome of K virus was found to be slightly smaller than that of polyoma virus, and the cleavage patterns of the viral DNAs with six restriction endonucleases were different. These findings indicate that there is little relationship between these two murine papovaviruses.
Topics: Antigens, Viral; BK Virus; Base Sequence; DNA Restriction Enzymes; DNA, Viral; Epitopes; Nucleic Acid Conformation; Papillomaviridae; Polyomaviridae; Polyomavirus; Simian virus 40
PubMed: 81318
DOI: 10.1128/JVI.28.1.337-343.1978 -
The Journal of Biological Chemistry Jun 1979A new approach for evaluating homologous sequences among related DNAs is presented. Conventional filter hybridization techniques are employed at 35 degrees C in a range... (Comparative Study)
Comparative Study
A new approach for evaluating homologous sequences among related DNAs is presented. Conventional filter hybridization techniques are employed at 35 degrees C in a range of formamide concentrations in order to perform annealings at effective temperatures as low as Tm -50 degrees C which permits the detection of regions of homology with as much as 33% base mismatch. Under such nonstringent conditions, high levels of specific annealing can be obtained at plateau levels. In combination with the Southern "blotting" technique (1975), this approach can be used to perform biochemical heteroduplex melting experiments. The homology among the genomes of the murine polyoma virus (Py), the simian virus 40 (SV40), and the human papovavirus BK was evaluated using this new methodology.
Topics: DNA, Viral; Genes, Viral; Kinetics; Nucleic Acid Hybridization; Polyomavirus; Simian virus 40; Species Specificity
PubMed: 220264
DOI: No ID Found -
The Journal of Biological Chemistry Feb 2002Sialic acids are critical components of many glycoconjugates involved in biologically important ligand-receptor interactions. Quantitative and structural variations of...
Sialic acids are critical components of many glycoconjugates involved in biologically important ligand-receptor interactions. Quantitative and structural variations of sialic acid residues can profoundly affect specific cell-cell, pathogen-cell, or drug-cell interactions, but manipulation of sialic acids in mammalian cells has been technically limited. We describe the finding of a previously unrecognized and efficient uptake and incorporation of sialic acid analogues in mammalian cells. We added 16 synthetic sialic acid analogues carrying distinct C-1, C-5, or C-9 substitutions individually to cell cultures of which 10 were readily taken up and incorporated. Uptake of C-5- and C-9-substituted sialic acids resulted in the structural modification of up to 95% of sialic acids on the cell surface. Functionally, binding of murine sialic acid-binding immunoglobulin-like lectin-2 (Siglec-2, CD22) to cells increased after N-glycolylneuraminic acid treatment, whereas 9-iodo-N-acetylneuraminic acid abolished binding. Furthermore, susceptibility to infection by the B-lymphotropic papovavirus via a sialylated receptor was markedly enhanced following pretreatment of host cells with selected sialic acid analogues including 9-iodo-N-acetylneuraminic acid. This novel experimental strategy allows for an efficient biosynthetic engineering of surface sialylation in living cells. It is versatile, extending the repertoire of modification sites at least to C-9 and enables detailed structure-function studies of sialic acid-dependent ligand-receptor interactions in their native context.
Topics: Animals; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Burkitt Lymphoma; Cell Adhesion Molecules; Clone Cells; Culture Media, Serum-Free; HL-60 Cells; Humans; Lectins; Mice; N-Acetylneuraminic Acid; Sialic Acid Binding Ig-like Lectin 2; Sialyltransferases; Substrate Specificity; Tumor Cells, Cultured
PubMed: 11751912
DOI: 10.1074/jbc.M109973200 -
Infection and Immunity Nov 1979Newborn mice were inoculated with a murine papovavirus, K virus, by intracranial, intraperitoneal, oral, and intranasal routes, and the pathogenesis of infection was...
Newborn mice were inoculated with a murine papovavirus, K virus, by intracranial, intraperitoneal, oral, and intranasal routes, and the pathogenesis of infection was studied with immunofluorescence, virus assay, and histopathology. Inoculation by each route produced a fatal interstitial pneumonia. Pulmonary vascular endothelium and, to a lesser extent, cells lining hepatic sinusoids were the major sites of viral replication, but intranuclear antigen or inclusions or both were also found in extrapulmonary vascular endothelia, spleens, lymph nodes, and brains. Although K virus produced a predominantly respiratory illness, the virus was less infectious by intranasal than by oral inoculation and did not replicate in respiratory epithelial tissues. The earliest site of K virus replication was the jejunal submucosa, suggesting that in nature K virus may be transmitted by the oral route. Viral antigen was present in brains of animals inoculated by each route and correlated with the duration of viremia. Despite the presence of abundant viral antigen, however, the nervous system remained morphologically normal. The present study indicates that a member of the papovavirus group may produce clinically silent, noninflammatory involvement of the central nervous system during the initial infection of its natural host.
Topics: Animals; Animals, Newborn; Fluorescent Antibody Technique; Mice; Papillomaviridae; Polyomaviridae; Pulmonary Fibrosis; Tumor Virus Infections; Virus Replication
PubMed: 397932
DOI: 10.1128/iai.26.2.705-713.1979 -
Journal of Virology Sep 1981The genome of MG virus, a variant of the human papovavirus BK virus, consists of two molecules, M1 and M2, M1 and M2 have deletions which correspond to 0.33 to 0.55 map... (Comparative Study)
Comparative Study
The genome of MG virus, a variant of the human papovavirus BK virus, consists of two molecules, M1 and M2, M1 and M2 have deletions which correspond to 0.33 to 0.55 map unit and 0.77 to 0.85 map unit, respectively, from the EcoRI site on the BK virus genome. Restriction enzyme analysis of the DNAs of these viruses revealed many alterations in both DNA species. Both M1 and M2 DNAs have three recognition sites for EcoRI. M1 has a single recognition site for HindIII and five sites for PvuII. M2 has a single recognition site for PuvII and three sites for HindIII. The sites of these and several other restriction enzymes on each DNA molecule were mapped after the cloning of M1 and M2 DNAs into pBR322 at their unique HindIII and PvuII sites, respectively.
Topics: BK Virus; DNA Restriction Enzymes; DNA, Viral; Genes, Viral; Humans; Nucleic Acid Hybridization; Papillomaviridae; Polyomaviridae; Polyomavirus
PubMed: 6270363
DOI: 10.1128/JVI.39.3.968-972.1981 -
Journal of Clinical Microbiology Apr 1978Simian papovavirus SA12 agglutinated human, guinea pig, and chicken erythrocytes. SA12 hemagglutinin was most effectively released from debris of infected tissue culture...
Simian papovavirus SA12 agglutinated human, guinea pig, and chicken erythrocytes. SA12 hemagglutinin was most effectively released from debris of infected tissue culture cells at an alkaline pH.
Topics: Animals; Antibody Formation; BK Virus; Cross Reactions; Haplorhini; Hemagglutination, Viral; Hydrogen-Ion Concentration; Polyomavirus; Simian virus 40
PubMed: 29051
DOI: 10.1128/jcm.7.4.396-398.1978