Merkel Cell Polyomavirus: Decoding Reference Sequences, miRNA, and the Oncogenic Roles of LT, LTtr, and sT in Merkel Cell Carcinoma

Merkel cell polyomavirus (MCPyV) is a virus that has been associated with Merkel cell carcinoma, an aggressive form of skin cancer. The MCPyV genome is small, circular, and double-stranded DNA with a length of approximately 5.4 kilobases. Here, we will provide a brief summary of the reference sequences of MCPyV isolates and the microRNA (miRNA) found in the virus.

• Reference sequence of MCPyV isolates: The reference sequence of MCPyV isolates can be found in the National Center for Biotechnology Information (NCBI) database. The NCBI's Genome database contains information on the complete MCPyV genome, which can be accessed using the following link: https://www.ncbi.nlm.nih.gov/datasets/genomes/?taxon=493803&utm_source=nuccore&utm_medium=referral

• MCPyV isolate WaGa: The MCPyV isolate WaGa (accession number: KJ128379.1) is a strain of the virus discovered in 2014. The complete genome of this isolate can be found in the NCBI's Nucleotide database at the following link: https://www.ncbi.nlm.nih.gov/nuccore/KJ128379.1

• MCPyV isolate MKL-1: The MCPyV isolate MKL-1 (accession number: FJ173815.1) is another strain of the virus, which was identified in 2008. The complete genome of this isolate is also available in the NCBI's Nucleotide database and can be accessed at the following link: https://www.ncbi.nlm.nih.gov/nuccore/FJ173815.1

• miRNA: MCPyV encodes a microRNA (miRNA) known as miR-M1 (accession number: JN707599.1). miRNAs are small, non-coding RNA molecules that play important roles in regulating gene expression. The sequence of miR-M1 can be found in the NCBI's Nucleotide database using the following link: https://www.ncbi.nlm.nih.gov/nuccore/JN707599.1

LT, LTtr, and sT are viral proteins that play critical roles in MCPyV-associated oncogenesis, specifically in the development of Merkel cell carcinoma, an aggressive form of skin cancer.

• LT (Large Tumor antigen): The Large Tumor antigen is a multifunctional protein encoded by MCPyV. It is involved in various cellular processes, including cell cycle regulation, DNA replication, and cell transformation. LT binds to the tumor suppressor protein retinoblastoma (Rb) and disrupts its function, leading to uncontrolled cell proliferation. In the context of MCPyV-associated Merkel cell carcinoma, LT expression is often observed in tumor cells, suggesting its importance in the development of this aggressive skin cancer.

• LTtr (Large Tumor antigen truncated): LTtr is a truncated version of the Large Tumor antigen, which is shorter than the full-length LT protein. This truncation results from a mutation or deletion in the viral genome, leading to a premature stop codon and an incomplete protein product. While LTtr retains some of the functions of the full-length LT, it may have altered activity or reduced functionality. The exact role of LTtr in MCPyV-associated Merkel cell carcinoma is still being investigated.

• sT, or Small Tumor antigen, is another protein encoded by Merkel Cell Polyomavirus (MCPyV) and is involved in MCPyV-related oncogenesis. sT is a multifunctional protein that plays various roles in cellular processes, including the activation of signaling pathways, modulation of protein stability, and the disruption of cellular functions that can contribute to cancer development.

  • One of the key roles of sT is its ability to interact with and inhibit protein phosphatase 2A (PP2A), a cellular tumor suppressor that negatively regulates cell growth and division. By inhibiting PP2A, sT promotes cell proliferation and survival, contributing to oncogenesis.

  • In addition to its interaction with PP2A, sT can also activate the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathway, which further supports cell survival and growth. Furthermore, sT has been found to induce the expression of heat shock proteins, which are associated with cellular stress responses and contribute to the stabilization of oncogenic proteins.

In MCPyV-associated Merkel cell carcinoma, both Large Tumor antigen (LT) and Small Tumor antigen (sT) are expressed in tumor cells, suggesting that they cooperatively contribute to the development of this aggressive skin cancer. While LT primarily targets the retinoblastoma (Rb) tumor suppressor protein, sT interacts with multiple cellular targets to promote cell growth and survival, ultimately leading to oncogenesis.

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