Selection against large T-antigen expression in cells transformed by lymphotropic papova virus

Hoyningen-Huene, V. von; Kurth, Marion; Deppert, Wolfgang

doi:10.1016/0042-6822(92)91201-5

Cited by 9 publications

(5 citation statements)

References 36 publications

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“…If this is the case, it would argue for the presence of a selectional pressure against MCPyV in some, but not all lines. In fact, detrimental effects of African Green Monkey Polyomavirus infection on cell growth in vitro with a subsequent decrease in viral copy numbers of integrated viral genomes has been observed previously 22. However, at least within the ∼4–6 month time period during which the lines were kept in continuous culture during our studies, we did not observe a further decline in viral copy numbers (data not shown).…”

Section: Discussionsupporting

confidence: 61%

Detection of Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma cell lines: Cell morphology and growth phenotype do not reflect presence of the virus

Fischer

Brandner

Fuchs

et al. 2009

Intl Journal of Cancer

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The recently discovered human polyomavirus (MCPyV) is frequently found in Merkel cell carcinoma (MCC) tissue and is believed to be causally linked to MCC pathogenesis. While cell lines established from MCC represent a valuable tool to study the contribution of MCPyV to MCC pathogenesis, hitherto only 1 MCPyV‐positive line has been described. We have analyzed 7 MCC cell lines for the presence, integration pattern and copy number of MCPyV. In 5 cell lines, MCPyV specific sequences were detected. In 3 of these lines, multiple copies of viral genomes per cell were detected, and sequencing of PCR amplificates identified distinct mutations predicted to lead to the expression of a truncated large T‐Antigen (LT‐Ag). In 1 cell line, clonal integration of concatamerized viral genomes was confirmed by Southern Blotting. MCC cell lines are conventionally categorized as “classic” or “variant” and further divided into 4 subtypes, based on expression of neuroendocrine markers and morphology. While it has been suggested that the presence of MCPyV might promote a classic phenotype, such a notion is not supported by our data. Instead, we find MCPyV‐positive as well as ‐negative lines of the classic variety, indicating that the distinguishing features are either inherently independent of viral infection or have become so in the course of tumorigenesis and/or cell line establishment. We therefore suggest a novel classification scheme based on MCPyV presence, integration patterns and T‐Ag mutations. The cell lines described here extend the repertoire of available MCPyV‐positive MCC‐lines and should aid in the elucidation of the role of MCPyV in the pathogenesis of MCC.

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Section: Discussionsupporting

confidence: 61%

Detection of Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma cell lines: Cell morphology and growth phenotype do not reflect presence of the virus

Fischer

Brandner

Fuchs

et al. 2009

Intl Journal of Cancer

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“…LPV is similar to other known polyomaviruses in terms of genome size, coding potential and genome organization (4, 5). Based on sequence homology of the LT proteins, LPV is a distant relative of both SV40 and MuPyV, but is closely related to the recently discovered human HuPy9 (6).…”

Section: Introductionmentioning

confidence: 79%

“…However, unlike SV40 LT, some results suggest that LPV LT may not be the essential oncoprotein mediating transformation. For instance, pools of cells transformed by SV40.ER express high levels of LT, but cells transformed via LPV.ER show low LT levels, perhaps because they become genetically unstable when expressing high LT levels and are thus eliminated by negative selection (4). We have performed an extended analysis of the different T antigen products encoded by LPV.ER and examined their ability to transform mouse embryo fibroblasts and found new properties of the T antigens encoded by LPV.…”

Section: Introductionmentioning

confidence: 99%

Expression of the small T antigen of Lymphotropic Papovavirus is sufficient to transform primary mouse embryo fibroblasts

et al. 2016

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Polyomaviruses induce cell proliferation and transformation through different oncoproteins encoded within the early region (ER): large T antigen (LT), small T antigen (sT) and, in some cases, additional components. Each virus utilizes different mechanisms to achieve transformation. For instance, the LTs of Simian virus 40 (SV40), BK and/or JC virus can induce transformation; but Merkel Cell Polyomavirus (MCPyV) requires expression of sT. Lymphotropic Papovavirus (LPV) is closely related to Human Polyomavirus 9 (HuPyV9) and, under similar conditions, mice expressing LPV.ER exhibit higher rates of tumor formation than mice expressing SV40.ER. We have investigated the contributions of individual LPV.ER components to cell transformation. In contrast to SV40, LPV.ER transforms mouse embryonic fibroblasts (MEFs), but expression of LPV LT is insufficient to transform MEFs. Furthermore, LPV sT induces immortalization and transformation of MEFs. Thus, in the case of LPV, sT is the main mediator of oncogenesis.

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“…The wt T‐Ag of SV40, the mutant cytoplasmic cT‐Ag variant (with a deletion of the SV40 nucleotide sequence 4490–4392, representing the nuclear localization signal (NLS)‐encoding amino acid sequence T110–152 or the N‐terminal T272 fragment were cloned into the BMGneo vector as described previously (18). The BMG/T411–708 construct was generated from the T‐Ag encoding plasmid pEARLY (19). The T411708‐encoding NsiI/BamHI fragment of pEARLY was cloned into the PstI/BamHI site of pBluescript (cat.…”

Section: Methodsmentioning

confidence: 99%

Priming polyvalent immunity by DNA vaccines expressing chimeric antigens with a stress protein‐capturing, viral J‐domain

et al. 2002

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The N-terminal domain of large tumor antigens (T-Ag) of polyomaviruses forms a DnaJ-like structure with a conserved J domain that associates with constitutively expressed stress protein heat shock protein (hsp)73. Mutant (but not wild-type) SV40 T-Ag show stable, ATP-dependent binding to the stress protein hsp73 when expressed in cells from different vertebrate tissues. Intracellular T/hsp73 complexes accumulate to high steady-state levels. From this observation, we designed a vector system that supports stable expression of a large variety of hsp73-capturing, chimeric antigens containing an N-terminal, T-Ag-derived domain, and different C-terminal antigenic domains from unrelated antigens. Most antigenic domains tested could be stably expressed only in eukaryotic cells as fusion protein/hsp73 complexes. The N-terminal 77 residues representing the J domain of T-Ag were required for stable hsp73 binding and efficient expression of chimeric antigens. Hsp73-bound chimeric antigens expressed by DNA vaccines showed strikingly enhanced immunogenicity evident in humoral (antibody) and cellular cytolytic T lymphocytes (CTL) responses. The described system supports efficient expression of chimeric, polyvalent antigens and their codelivery with hsp73 as a "natural adjuvant" for enhanced immunogenicity for T and B cells.

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Selection against large T-antigen expression in cells transformed by lymphotropic papova virus

Cited by 9 publications

References 36 publications

Detection of Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma cell lines: Cell morphology and growth phenotype do not reflect presence of the virus

Detection of Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma cell lines: Cell morphology and growth phenotype do not reflect presence of the virus

Expression of the small T antigen of Lymphotropic Papovavirus is sufficient to transform primary mouse embryo fibroblasts

Priming polyvalent immunity by DNA vaccines expressing chimeric antigens with a stress protein‐capturing, viral J‐domain

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