Characterization of monoclonal antibodies specific for the Merkel cell polyomavirus capsid

Pastrana, Diana V.; Pumphrey, Katherine A.; Çuburu, Nicolas; Schowalter, Rachel M.; Buck, Christopher B.

doi:10.1016/j.virol.2010.06.022

Cited by 20 publications

(24 citation statements)

References 41 publications

(49 reference statements)

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“…Monoclonal antibody Xt7 was raised by priming mice with recombinant HPyV10 sT fused to maltose binding protein followed by boosting with His-tagged recombinant HPyV10 J-domain. Hybridomas were generated and screened as described (15). Validation experiments revealed that Xt7 cross-reacts with the J-domain of a wide variety of polyomavirus LT proteins, including LPV.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…Hemagglutination and basement membrane extract experiments used unlabeled capsids, while cell-binding studies used capsids covalently conjugated to Alexa Fluor 488 using previously-reported methods [53]. For production of Alexa Fluor 488 labeled capsids, a reporter plasmid encoding Gaussia luciferase (phGluc; [25]) was included in the initial transfection mixture.…”

Section: Methodsmentioning

confidence: 99%

Glycosaminoglycans and Sialylated Glycans Sequentially Facilitate Merkel Cell Polyomavirus Infectious Entry

2011

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Merkel cell polyomavirus (MCV or MCPyV) appears to be a causal factor in the development of Merkel cell carcinoma, a rare but highly lethal form of skin cancer. Although recent reports indicate that MCV virions are commonly shed from apparently healthy human skin, the precise cellular tropism of the virus in healthy subjects remains unclear. To begin to explore this question, we set out to identify the cellular receptors or co-receptors required for the infectious entry of MCV. Although several previously studied polyomavirus species have been shown to bind to cell surface sialic acid residues associated with glycolipids or glycoproteins, we found that sialylated glycans are not required for initial attachment of MCV virions to cultured human cell lines. Instead, glycosaminoglycans (GAGs), such as heparan sulfate (HS) and chondroitin sulfate (CS), serve as initial attachment receptors during the MCV infectious entry process. Using cell lines deficient in GAG biosynthesis, we found that N-sulfated and/or 6-O-sulfated forms of HS mediate infectious entry of MCV reporter vectors, while CS appears to be dispensable. Intriguingly, although cell lines deficient in sialylated glycans readily bind MCV capsids, the cells are highly resistant to MCV reporter vector-mediated gene transduction. This suggests that sialylated glycans play a post-attachment role in the infectious entry process. Results observed using MCV reporter vectors were confirmed using a novel system for infectious propagation of native MCV virions. Taken together, the findings suggest a model in which MCV infectious entry occurs via initial cell binding mediated primarily by HS, followed by secondary interactions with a sialylated entry co-factor. The study should facilitate the development of inhibitors of MCV infection and help shed light on the infectious entry pathways and cellular tropism of the virus.

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“…Although one study (25) reports the presence of viral particles by electron microscopy in two of five MCCs, robust antibodies developed against the late capsid protein viral protein 1 (VP1) universally show that tumor cells are negative (26, 27). …”

Section: Merkel Cell Carcinoma and Merkel Cell Polyomavirusmentioning

confidence: 99%

Merkel Cell Carcinoma: A Virus-Induced Human Cancer

Chang

Moore

2012

Annu. Rev. Pathol. Mech. Dis.

181

183

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Merkel cell polyomavirus (MCV) is the first polyomavirus directly linked to human cancer, and its recent discovery helps to explain many of the enigmatic features of Merkel cell carcinoma (MCC). MCV is clonally integrated into MCC tumor cells, which then require continued MCV oncoprotein expression to survive. The integrated viral genomes have a tumor-specific pattern of tumor antigen gene mutation that incapacitates viral DNA replication. This human cancer virus provides a new model in which a common, mostly harmless member of the human viral flora can initiate cancer if it acquires a precise set of mutations in a host with specific susceptibility factors, such as age and immune suppression. Identification of this tumor virus has led to new opportunities for early diagnosis and targeted treatment of MCC.

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Characterization of monoclonal antibodies specific for the Merkel cell polyomavirus capsid

Cited by 20 publications

References 41 publications

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

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

Glycosaminoglycans and Sialylated Glycans Sequentially Facilitate Merkel Cell Polyomavirus Infectious Entry

Merkel Cell Carcinoma: A Virus-Induced Human Cancer

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