Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission

Abstract

Merkel Cell Virus (MCV) is a newly discovered polyomavirus, recently found in a rare skin cancer, Merkel cell carcinoma (MCC). However, MCV has also been detected in some normal tissue samples. We tested and compared the relative quantity of the MCV in a set of diverse human tissue samples with the MCC samples. The levels of MCV in MCCs were over 60 times higher than the highest values in all other tissues. Low quantities of MCV were detected in diverse tissue samples independently of malignant or benign histologic status. Higher levels of the virus were found in the upper aerodigestive tract, digestive system, and saliva compared to the lung and genitourinary system samples. These results confirm that MCV is widespread in the human body and suggest a possible fecal-oral transmission route similar to the Hepatitis A virus. Despite widespread presence of the virus, it appears that only neuroendocrine skin cells are susceptible to transformation by MCV.Merkel cell carcinomas (MCC) are rare neuroendocrine skin tumors that develop from neuroendocrine cells responsible for the sense of touch and pressure. The incidence of MCC has tripled over the past 20 years to about 1,500 cases a year. Increased ascertainment has at least in part contributed to this rise in incidence. People at risk include those with fair skin, excessive sunlight exposure, and a history of numerous nonmelanoma skin cancers. Additionally, patients under immunosuppression including solid organ transplant recipients, and patients with altered lymphocytic function such as patients with AIDS, lymphoma, and leukemia appear to be predisposed to MCC.

Low prevalence of Merkel cell polyomavirus with low viral loads in oral and maxillofacial tumours or tumour-like lesions from immunocompetent patients: Absence of Merkel cell polyomavirus-associated neoplasms

“…However, previous studies on the frequency of MCPyV infection in oral tumours or tumour-like lesions are partial and incomplete (7,15). High viral loads of MCPyV were detected in all saliva samples from 10 patients without cancer (7).…”

“…The possibility of contamination was unlikely, as ultrapure water-negative controls were consistently negative. Loyo et al (7) reported data on MCPyV DNA prevalence in oral cavity fresh-frozen materials (51/67, 76%); the prevalence was 19/47 SCCs, 2/10 normal mucosal samples and 10/10 saliva samples from patients without cancer. Oral cavity samples had 0.026 copies/genome, while MCCs had an average of 10 copies/genome (range, 173-0.05 copies̸genome) and saliva had an average of 0.128 copies/genome (range, 5-0.01) (7).…”

“…Moreover, certain investigators have reported that low viral loads of MCPyV have also been detected in normal human tissue samples, including skin, liver and respiratory secretions, suggesting that this virus is widespread in the human body (7,17). However, previous studies on the frequency of MCPyV infection in oral tumours or tumour-like lesions are partial and incomplete (7,15). High viral loads of MCPyV were detected in all saliva samples from 10 patients without cancer (7).…”

“…MCPyV has been detected in MCC patients and appears to play a key role in tumourigenesis; ~80% of MCCs harbour MCPyV (1). Using quantitative polymerase chain reaction (qPCR), MCPyV has been detected in malignant and benign tumours (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Moreover, certain investigators have reported that low viral loads of MCPyV have also been detected in normal human tissue samples, including skin, liver and respiratory secretions, suggesting that this virus is widespread in the human body (7,17).…”

Human Merkel cell polyomavirus: virological background and clinical implications

“…The MCPyV viral load on the skin surface varies from less than 1 copy per 1000 cells to 1000 copies per cell (9,26,30,(39)(40)(41). The mean DNA copy per cell in normal skin has been reported to be 0.02-0.07 (42).…”