Detection of Merkel Cell Polyomavirus in the Human Tissues from 41 Japanese Autopsy Cases Using Polymerase Chain Reaction

Abstract

It has recently been shown that approximately 80% of Merkel cell carcinomas harbor a novel polyomavirus named Merkel cell polyomavirus (MCPyV). MCPyV has been detected in human tissue samples. However, detailed distribution of MCPyV in non-neoplastic Japanese human tissues remains unclear. To address this, we used single or real-time quantitative polymerase chain reaction (PCR) for 41 autopsy cases. PCR revealed MCPyV-DNA in non-neoplastic samples: total, 29/41 (71%); adult, 29/39 (74%); fetus or infant, 0/2; men, 24/28 (86%); women, 5/13 (38%); total human tissues, 66/572 (12%); skin, 8/15 (53%); adrenal gland, 9/33 (27%), and other 16 organs (4–25%). This study first reported the presence of MCPyV-DNA in non-neoplastic tissues of thyroid gland, adrenal gland, spleen, bone marrow, stomach, gallbladder, pancreas, heart, and aorta. PCR revealed that viral load ranged from 0.00026 to 0.22 in all MCPyV-positive tissues compared with Merkel cell carcinoma samples. These detailed PCR data showed higher prevalence of MCPyV infection in Japanese men than women (p = 0.004) and broad distribution of MCPyV with low viral load in more non-neoplastic human tissues than in the previous reports. These data provide valuable insights for further studies of MCPyV infection and MCPyV-related diseases.

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

“…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). Matsushita et al (17) did not detect MCPyV DNA in non-neoplastic tissues from 10 tongue samples and 2 salivary gland samples from FFPE sections of autopsy cases. The MCPyV prevalence in the present study was 7.0% (23/327).…”

“…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). However, previous studies on the frequency of MCPyV infection in oral tumours or tumour-like lesions are partial and incomplete (7,15).…”

Age and Gender Associations of Virus Positivity in Merkel Cell Carcinoma Characterized Using a Novel RNA In Situ Hybridization Assay

“…Wild-type MCPyV may reside in skin and other tissues, with a high prevalence of infection in the general population (15,26,27). MCPyV-associated MCC is thought to arise in the rare event when MCPyV aberrantly integrates into the genome of the tumor progenitor cell and undergoes truncation or mutation of the LTAg gene that renders the virus replication-deficient but transformation-competent (2).…”

“…In addition, qPCR does not allow for direct correlation with tissue morphology, hence preventing confirmation of adequate tumor content and localization of signal to tumor cells. This is relevant because qPCR may detect the presence of wild-type MCPyV in various tissues (27), and reliable cutoffs have not been demonstrated for distinguishing background MCPyV infection from tumor MCPyV. Hence, there is potential for false positive results by qPCR.…”

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).…”