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A Corallini

Publications and source records attributed to A Corallini.

At least 55 records · Page 3Linked to original sources
PubMed1986

Molecular and biological properties of BK virus-IR, a BK virus variant isolated from a human tumor.

We describe the molecular and biological properties of BK virus (BKV)-IR, a new BKV variant isolated from a human tumor of pancreatic islets. BKV-IR bears a 253-base-pair (bp) deletion and an 80-bp insertion in the early region of the genome. The deletion abolishes the expression of small-t antigen. The inserted sequences, grouped in four clusters, produce rearrangements in the first and second enhancer elements. They are bound by 12-bp direct repeats and could form a 217-base stem-loop structure suggestive of an insertion sequence. As compared with wild-type BKV, BKV-IR transformed hamster cells with a reduced efficiency and induced ependymomas in hamsters at a lower frequency and with a longer latency period. Tumors induced by BKV-IR, however, showed features of higher malignancy. The possible role of the insertion sequence-like element in transformation by BKV-IR is discussed.

Adenoma, Islet Cell↗
PubMed1985

Histologic, immunofluorescence, and ultrastructural study of malignant islet-cell tumors of the pancreas induced in hamsters by BK human papovavirus.

Histologic, immunofluorescence and ultrastructural studies were performed in 17 cases of pancreatic carcinomas induced by the BK virus in Syrian hamsters, a unique model of experimentally induced malignant islet cell tumors. The tumors were composed of small, poorly differentiated cells mostly arranged in a trabecular structure. By immunofluorescence all four islet cell types were found in the tumors, though with different frequency. Insulin cells were present in 16 cases, glucagon cells in 11, somatostatin cells in 7, PP cells in 6. Thirteen tumors contained more than one cell type. Insulin cells were the most frequent cell type in 13 cases, and glucagon cells predominated in 1 case. Insulin-containing cells usually occupied a central position within tumor-cell aggregates, while the other cell types were mostly located in a peripheral position, a distribution reminiscent of that seen in normal islets. Gastrin and calcitonin immunoreactivities were not observed. Immunoreactive cells were more abundant in tumors with trabecular structure. Argyrophil cells revealed by the Grimelius method often exceeded the cumulative number of immunoreactive cells in the same tumor, which suggests that there were additional cell types. Multiple cell types were also found in liver metastases. Ultrastructurally most neoplastic cells were poorly granulated. The occurrence of many damaged cells suggests hormone leakage, which may account, at least in part, for the deregulated hormone release from the tumors.

Adenoma, Islet Cell↗
PubMed1985

Restricted replication of BK virus in human lymphocytes.

Human lymphocytes from either peripheral blood or continuous cultures (P3HR-1 cells) are able to support the replication of prototype polyomavirus BK (BKV) as well as its related strain BO15 virus (BO15V). Instead, human monocytes from peripheral blood, although able to bind and egulf BKV virions, do not express virus-specific antigens within a 50 day observation period. In the light of these results, a probable role is suggested for human mononuclear blood cells in the mechanism of natural infection by polyomaviruses.

Antigens, Viral↗
PubMed1984

BK virus-plasmid expression vector that persists episomally in human cells and shuttles into Escherichia coli.

We describe a novel expression vector, pBK TK-1, that persists episomally in human cells that can be shuttled into bacteria. This vector includes sequences from BK virus (BKV), the thymidine kinase (TK) gene of herpes simplex virus type 1, and plasmid pML-1. TK+-transformed HeLa and 143 B cells contained predominantly full-length episomes. There were typically 20 to 40 (HeLa) and 75 to 120 143 B vector copies per cell, although some 143 B transformants contained hundreds. Low-molecular-weight DNA from TK+-transformed cells introduced into Escherichia coli were recovered as plasmids that were indistinguishable from the input vector. Removal of selective pressure had no apparent effect upon the episomal status of pBK TK-1 molecules in TK+-transformed cells. BKV T antigen may play a role in episomal replication of pBK TK-1 since this viral protein was expressed in TK+ transformants and since a plasmid that contained only the BKV origin of replication was highly amplified in BKV-transformed human cells that synthesize BKV T antigen.

BK Virus↗
PubMed1983

Episomal DNA of a BK virus variant in a human insulinoma.

BK virus (BKV) DNA was detected by blot hybridization in a human adenoma of pancreatic islets from patient I.R. BKV DNA was free, and no evidence was found of viral sequences integrated into cellular DNA. Virus was rescued by transfection of human embryonic fibroblasts with tumor DNA. The DNA from rescued virus (BKV-IR) was different from wild-type BKV DNA by restriction endonuclease mapping. The genome of BKV-IR is 235 base pairs (bp) shorter than the genome of wild-type BKV. This alteration originates from a deletion of approximately 300 bp involving HindIII fragments B and D, and an insertion of 70 bp in the region of HindIII fragment C. Transformation of hamster kidney cells was induced by total tumor DNA as well as by BKV-IR and BKV-IR DNA. No antibodies to BKV tumor (T) antigen were detected in the patient's serum by immunofluorescence. The significance of episomal BKV DNA in a human tumor is discussed.

Adenoma, Islet Cell↗
PubMed1983

BK virus-induced tumors in hamsters: a morphological, histochemical and ultrastructural study.

Macroscopic morphology, histology and ultrastructure of BK virus (BKV)-induced hamster and mouse tumors were investigated. Groups of animals were immunosuppressed to study the relationship between immune system and BKV oncogenesis. Ependymomas had the highest incidence, followed by tumors of pancreatic islets, osteosarcomas, lymphomas and sarcomas, sometimes associated in the same animal. All the tumors were found to be BKV specific. Ependymomas showed the shortest latency, infiltrated surrounding tissues but did not metastasize. Pseudo-rosettes were common and basal bodies were observed. Atypia and necrosis were more often present in immunosuppressed animals both for the ependymomas and for the other oncotypes. Pancreatic insulomas were frequently multinodular, possibly because of multifocal origin and metastasized to the liver. Hormone secretory granules were often found on electron microscopy. Osteosarcomas metastasized to lungs and peritoneum and showed the presence of osteoid, chondroblastoid and mixoid areas. Characteristic giant cells were present. Immunosuppression did not enhance tumor incidence and did not influence the latency period. However, neoplastic growth appeared to be more rapid and with more aggressive behavior in immunodepressed animals. These findings suggest an influence of the immune system in tumor development, whereas the virus oncogenic process seems unaffected.

Animals↗
PubMed1983

Formation of oligomeric free BK virus DNA is required for tandem integration of viral genomes into cellular DNA.

Mouse kidney cells have been transformed by linear BK virus (BKV) DNA with cohesive ends. These BKV genomes can circularize and subsequently replicate or physically join end to end yielding oligomeric viral DNA molecules. Blot hybridization analysis of transformed cells showed the presence of BKV DNA both in free circular forms and integrated into cellular DNA in a tandem head-to-tail array of full-length viral genomes. Formation of oligomers either by replication via previous circularization or by end to end joining is hindered after elimination of cohesive termini by digestion with the single-strand-specific nuclease S1. After treatment of linear BKV DNA with nuclease S1 only integrations of single viral genomes were observed in transformed cells; tandem insertions and free viral DNA were absent. These results support the hypothesis that formation of tandems of free viral DNA is a necessary prerequisite for tandem integration of viral genomes.

Animals↗
PubMed1982

Oncogenity of BK virus for immunosuppressed hamsters.

Tumors were induced by BK virus (BKV) inoculated intravenously in 3-week-old Syrian golden hamsters immunosuppressed with anti-lymphocyte serum or methylprednisolone acetate alone or in association with gamma-radiation (60Co). The induced neoplasms were ependymoma, carcinoma of pancreatic islets, lymphoma, osteosarcoma, undifferentiated sarcoma, kidney and renal pelvis carcinoma, pheochromocytoma and hemangiosarcoma. High levels of insulin and glucagon and altered concentrations of glucose were detected in blood of animals with tumors of pancreatic islets. No antibodies to BKV tumor antigen (TAg) and low levels of hemagglutination-inhibition antibodies to BKV viral coat protein Ag were detected in hamster sera. BKV TAg was found in tumors by complement fixation. Blot hybridization analysis of tumor DNA showed the presence of both free and integrated BKV genomes in tumor cells. BKV DNA inoculated intravenously and subcutaneously in immunosuppressed or immunocompetent hamsters was not oncogenic, whereas it was weakly oncogenic when inoculated intracerebrally.

Animals↗
PubMed1982

Transformation of human embryonic fibroblasts by BK virus, BK virus DNA and a subgenomic BK virus DNA fragment.

Human embryonic fibroblasts (HEF) have been transformed by BK virus (BKV) DNA and by u.v.-inactivated or live BKV alone or in association with methyl-cholanthrene (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 Vero 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.

Antigens, Viral↗
PubMed1982

Transformation of hamster kidney cells by fragments of BK virus DNA.

Hamster kidney cells were transformed, with comparable efficiency, by circular or linear molecules of complete BK virus (BKV) genome and by agarose gel-purified fragments of BKV DNA obtained by single or double digestions with various restriction endonucleases. Only fragments containing the complete early region of BKV DNA displayed transforming activity. Analysis by blot hybridization of the arrangement of viral DNA sequences in a cloned cell line transformed by a 3.8-kilobase fragment, obtained after sequential digestion of BKV DNA with HhaI and BamHI, showed the presence of seven viral integrations into the cellular DNA. Apparently all of the integrated viral molecules contained the entire early region of BKV DNA. Large T antigen, small t antigen, and the 56,000-dalton nonviral Tau antigen were detected in transformed cells by immunoprecipitation. The pattern of integration of viral sequences in transformed cells was constant over many generations. Likewise, large T antigen was always detected in transformed cells at various passage levels. These results may suggest that all of the sequences of the early region coding for large T antigen are required for transformation by BKV. Alternatively, subgenomic segments of the BKV DNA early region may be unable to transform because the appropriate polyadenylation site, necessary to obtain a complete functional transcriptional unit, is removed by the restriction enzyme cleavage.

Animals↗
PubMed1981

[Preliminary observations on in vitro biosynthesis of prostaglandins E in tumor cells and virus transformed cells].

Biosynthesis of prostaglandins of E series in BK virus-transformed rabbit-kidney cells (RKBK) and mouse hepatoma cells cultured in vitro with and without exogenous arachidonic acid was determined by radioimmunoassay. Elevated concentrations of prostaglandin E2 were observed in both cell types; moreover, tumor and transformed cells were capable to synthesize higher levels of prostaglandin E2 than normal cells. Mouse hepatoma cells produced more prostaglandins compared to RKBK cells; in addition they seemed less sensitive to inhibition by indomethacin. These data suggest that arachidonic acid metabolism may be another one of the intrinsic biochemical properties that differentiate tumor and virus transformed cells.

Animals↗
PubMed1981

Analysis of BK virus-transformed cells and BK virus-induced tumors by DNA-DNA reassociation kinetics.

BK virus (BKV)-transformed cells and BKV-induced tumors as well as in vitro derived tumor cell lines were all found to contain BKV DNA sequences when analysed by DNA-DNA reassociation kinetics. In transformed cells the number of viral genome equivalents per diploid cell genome (CG divided by VG) decreased with increasing generations. Likewise, single cell clones had a lower CG divided by VG than parental transformed cells. BKV-induced tumors had a high CG divided by VG. Tumor cells cultivated in vitro and their clones had a lower CG divided by VG than BKV-induced tumors from which they were derived, suggesting a multiclonal origin of tumors. Hamster tumors induced by subcutaneous inoculation of BKV-transformed cells or tumor cell lines had a higher CG divided by VG than cells producing them. Variation in CG divided by VG is discussed in terms of cell selection depending on different in vitro or in vivo conditions of cell growth. In some cases, however, the decrease in CG divided by VG most likely depends on loss on free viral sequences from transformed cells or tumors.

Animals↗
PubMed1981

Lack of association between BK virus and ependymomas, malignant tumors of pancreatic islets, osteosarcomas and other human tumors.

BK virus (BKV) DNA sequences were not detected in 142 human tumors analyzed by DNA-DNA reassociation kinetics and blot hybridization. The investigation was focused mainly on those rare types of human tumors (ependymomas, choroid plexus papillomas, tumors of pancreatic islets and osteosarcomas) that are induced with highest frequency by BKV in experimental animals. In addition, other tumors of the urinary apparatus and of the central nervous system were analyzed. BKV tumor (T) antigen was not detected in neoplastic tissues, and BKV T antibodies were not found in sera and cerebrospinal fluids from patients with neoplasms. Sequences homologous to BKV DNA were found in normal tissue from a kidney carrying a carcinoma. The neoplastic tissue from the same organ, however, had no sequences homologous to BKV DNA. Such DNA does not belong to BKV but probably to another papovavirus related to BKV.

Antibodies, Viral↗
PubMed1980

Integrated and free viral DNA in hamster tumors induced by BK virus.

BK virus (BKV)-induced tumors in hamsters were investigated for the presence of viral DNA by the blot-transfer hybridization technique. Several viral genomes per cell were found in tumor tissues and in their derived cell lines and clones. Most of the detected viral genomes were integrated into the cellular DNA, but some tumors also contained free viral DNA sequences. Integration patterns were different from each other, and many different integration sites were available on the cellular or on the viral DNA or on both. Typical features of integration patterns were found in ependymomas, which were the most frequent (72%) among BKV-induced tumors. Readily detectable viral DNA sequences were only found in neoplastic tissues, but traces of BKV DNA were also present in the apparently normal portion of the brain of an animal that had developed an ependymoma and in the brain (but not in the liver) of another animal 15 days after virus inoculation. A cell line and a single-cell clone derived from a tumor had hybridization patterns considerably simpler that the pattern of the original tumor, lacking several integrated viral genomes and all free viral sequences.

Adenoma, Islet Cell↗
PubMed1980

BK papovavirus immune complexes in glomerulonephritis.

Kidney biopsies from 98 patients were studied for BK virus (BKV) antigens by indirect immunofluorescence. Intense fluorescent staining was observed in 11/12 cases of lupus nephritis, 11/12 cases of membranous nephropathy, 21/23 cases of IgA mesangial glomerulonephritis, 3/4 cases of membrano-proliferative Glomerulonephritis and 5/12 cases of exudative glomerulonephritis. Antisera of different viruses did not react with any kidney sample. Deposition of BKV was strictly related to the presence of immunoglobulins in renal glomeruli. The specificity of reaction for antigens related to BKV was demonstrated by absorption of sera with different substances and BKV. Absorption of rabbit anti-BKV serum with human immunoglobulins completely abolished glomerular fluorescence. We conclude that the fluorescence obtained in kidney biopsies by staining with anti-BKV serum was a false positive reaction dependent on common antigenic determinants present in BKV capsid proteins and human immunoglobulins.

Antigen-Antibody Complex↗