Merkel Cell Polyomavirus: Molecular Insights into the Most Recently Discovered Human Tumour Virus

Abstract

A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such cancer is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, Merkel cell polyomavirus (MCPyV) was discovered as the causative agent of MCC. It is found clonally integrated into the majority of MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun to reveal the molecular virology of MCPyV, as well as how it induces tumourigenesis. It is thought to be a common skin commensal, found at low levels in healthy individuals. Upon loss of immunosurveillance, MCPyV reactivates, and a heavy viral load is associated with MCC pathogenesis. Although MCPyV is in many ways similar to classical oncogenic polyomaviruses, such as SV40, subtle differences are beginning to emerge. These unique features highlight the singular position MCPyV has as the only human oncogenic polyomavirus, and open up new avenues for therapies against MCC.

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients

“…These findings are compatible with the mechanistic role that ultraviolet radiation plays in Merkel cell carcinogenesis. Immunosuppressed patients (14/61 (data missing for three patients)) comprised 23% of the patient cohort, which is certainly an overrepresentation compared to the general public, and is consistent with the role that Merkel cell polyomavirus plays in tumorigenesis, as well as the role of immunosurveillance in the elimination of occult cancers (16, 17). Overall, 28 of 62 patients with follow-up had tumor recurrence (45%, not shown).…”

Prediction and Conservancy Analysis of Multiepitope Based Peptide Vaccine Against Merkel Cell Polyomavirus: An Immunoinformatics Approach

“…MCPYV belongs to the Orthopolyomavirus genus of the Polyomaviridae family, which include mammalian polyomaviruses such as murine PyV (MPyV), simian virus (SV40) and the human polyomaviruses JC (JCPyV) and BK (BKPyV) [1][2][3][4][5][6][7][8][9][10][11]. The genome is 5.4 kb which constitute two regions; the early region which encodes the large tumor (T) and small T antigens, and the late region which comprise the structural viral proteins VP1, VP2 and VP3, which form the viral capsid.…”

“…The genome is 5.4 kb which constitute two regions; the early region which encodes the large tumor (T) and small T antigens, and the late region which comprise the structural viral proteins VP1, VP2 and VP3, which form the viral capsid. [2][3][4][5], However, VP1 makes up more than 70% of the total protein content of virus particles and is also called the major structural protein which is responsible for immunogenic response inside the host body [4,10]. Antibodies against vp1 protein is likely to be expressed in 90% of MCC tumors [11], thus it represent an ideal therapeutic candidate for designing immunoprophylactic vaccine [10,12,13].…”

“…Merkel cell carcinoma is an aggressive lethal neuroectodermal malignancy arising from mechanoreceptor Merkel cells [3,6,11,14,15]. MCC was first described by Cyril Toker in 1972, who noted a colored painless solid nodule within five different areas of two older men, who later died as a result of this tumor, and three older women, yet the pathogenesis and etiology of MCC remains poorly understood [3,6].…”

“…MCC was first described by Cyril Toker in 1972, who noted a colored painless solid nodule within five different areas of two older men, who later died as a result of this tumor, and three older women, yet the pathogenesis and etiology of MCC remains poorly understood [3,6]. MCC is rare, but its incidence has tripled over the past two decades in the United States to 1500 cases per year and 2,500 new cases diagnosed in the E.U [11,14,16].…”