Merkel Cell Polyomavirus and Merkel Cell Carcinoma

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 903

Special Issue Editors

Department of Public Health and Infectious Diseases, “Sapienza” University, Rome, Italy
Interests: polyomavirus and polyomavirus-associated diseases; polyomavirus reactivation under immunosuppression or during immunomodulatory therapy; polyomavirus involved in cancer transformation; development of in vitro models
Special Issues, Collections and Topics in MDPI journals
Department of Public Health and Infectious Diseases, “Sapienza” University, Rome, Italy
Interests: polyomaviridae family; polyomavirus-associated diseases in humans; evaluation of predictive biomarkers to manage polyomavirus infection and reativation in immunodepressed patients or in patients treated with different disease-modifying therapies; study of the polyomaviruses’s contribution into the development of cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer that frequently metastasizes into draining lymph nodes and distant organs. Accumulating evidence suggests that MCC pathogenesis could be associated with the presence of Merkel cell polyomavirus (MCPyV), a small non-enveloped DNA virus, characterized by a circular double-stranded genome encompassing three functional domains, a non-coding control region (NCCR), and the early and late regions.

The NCCR contains the viral origin (Ori) of replication and bidirectional promoters for the viral transcription of the early and late regions. The late region encodes for two capsid proteins, virus protein 1 (VP1) and virus protein 2 (VP2). The early region contains the “Tumor” (T) antigen gene locus, from which alternatively spliced RNA transcripts are produced. This region encodes for the large T (LT), small (sT), 57kT antigens, and for a product from an alternate frame of the LT open reading frame (ALTO). The MCPyV LT antigen contains motifs and domains, playing a prominent role in viral genome replication, transcription, and tumorigenesis. sT also contributes to tumorigenesis, whereas the functions of 57kT and ALTO remain obscure. To date, the link between MCPyV infection and cell transformation still needs to be clarified, although it has been established that viral DNA integration into the host genome and expression of the C-terminal truncated LT are required for MCC development. The C-terminus of LT contains anti-tumorigenic properties and may explain why this region is deleted in MCC.

It has been established that ~80% of the MCC-harbored MCPyV genome is clonally integrated. Before the large use of CK20 immunostaining, the pathology diagnosis was difficult and required electronic microscopy; thus, true MCC were frequently misclassified. MCC can also occur in association with UV-radiation–induced alterations involving mutations, heterozygous deletion, and hypermethylation of the Retinoblastoma gene. MCPyV and UV represent two different etiological inputs sharing clinical, histopathological, and prognostic similar features, although with different prognosis. Recently, it has been reported that MCPyVpositive MCCs show less metastatic tendency and better prognosis than MCPyV-negative MCCs. However, considering the widespread prevalence of the virus across the body, the involvement of MCPyV in tumors other than MCC cannot be excluded. It has been proposed that MCPyV could be associated with non-MCC cancers such as non-small-cell lung carcinoma (NSCLC).

In this Special Issue of Viruses, we want to explore some aspects to better understand MCPyV involvement in MCC pathogenesis and in tumors other than MCC, investigating the structure and life cycle, cell tropism, and the epidemiology of the virus and its oncogenic properties. Putative strategies to prevent viral infection or treat virus-positive Merkel cell carcinoma patients are welcome.

Prof. Dr. Valeria Pietropaolo
Dr. Carla Prezioso
Guest Editors

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Keywords

  • merkel cell polyomavirus (MCPyV)
  • merkel cell carcinoma (MCC)
  • non-MCC cancers
  • biomarkers
  • cell tropism
  • signaling pathways
  • therapy
  • transgenic mice
  • tumorigenesis
 

Published Papers (1 paper)

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Review

20 pages, 1280 KiB  
Review
Phosphorylation of Human Polyomavirus Large and Small T Antigens: An Ignored Research Field
by Ugo Moens, Sara Passerini, Mar Falquet, Baldur Sveinbjørnsson and Valeria Pietropaolo
Viruses 2023, 15(11), 2235; https://doi.org/10.3390/v15112235 - 09 Nov 2023
Viewed by 674
Abstract
Protein phosphorylation and dephosphorylation are the most common post-translational modifications mediated by protein kinases and protein phosphatases, respectively. These reversible processes can modulate the function of the target protein, such as its activity, subcellular localization, stability, and interaction with other proteins. Phosphorylation of [...] Read more.
Protein phosphorylation and dephosphorylation are the most common post-translational modifications mediated by protein kinases and protein phosphatases, respectively. These reversible processes can modulate the function of the target protein, such as its activity, subcellular localization, stability, and interaction with other proteins. Phosphorylation of viral proteins plays an important role in the life cycle of a virus. In this review, we highlight biological implications of the phosphorylation of the monkey polyomavirus SV40 large T and small t antigens, summarize our current knowledge of the phosphorylation of these proteins of human polyomaviruses, and conclude with gaps in the knowledge and a proposal for future research directions. Full article
(This article belongs to the Special Issue Merkel Cell Polyomavirus and Merkel Cell Carcinoma)
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