Merkel cell polyomavirus and trichodysplasia spinulosa-associated polyomavirus DNAs and antibodies in blood among the elderly

Merkel cell polyomavirus and trichodysplasia spinulosa-associated polyomavirus DNAs and antibodies in blood among the elderly

Merkel cell polyomavirus (MCPyV) and trichodysplasia spinulosa-associated polyomavirus (TSPyV) are recently found pathogens causing two rare skin disorders, Merkel cell carcinoma (MCC) and trichodysplasia spinulosa (TS). MCC is proportionally common in the elderly and most often is associated with immunosuppression.

TS is a folliculocentric infection seen in patients in an immunocompromised state. Little or no baseline information exists, however, on the prevalences of these two viruses among the elderly.

Epidemiologic data on this population could help in understanding their natural biology. We wished to determine the occurrences and blood levels of MCPyV and TSPyV DNAs among the elderly and any association between the prevalences of their corresponding antiviral IgG antibodies. 

Methods: From 394 hospitalized elderly individuals (age >=65 years) with respiratory symptoms, cardiovascular, and other diseases, we studied 621 serum samples by four different real-time quantitative (q) PCRs, two for the DNAs of MCPyV and two for TSPyV.

The IgG antibodies for both viruses among 481 serum samples of 326 subjects were measured with enzyme immunoassays (EIAs), using as antigen recombinant virus-like particles (VLPs). 

Results: Of the 394 patients, 39 (9.9%) were positive at least once for MCPyV DNA by the LT PCR, and 33 (8.4%) by the VP1 PCR, while 6 (1.5%) were positive by both PCR assays. In general, the viral DNA copy numbers were low.

In sharp contrast, no TSPyV DNA was detectable with qPCRs for the corresponding genomic regions. The IgG seroprevalence of MCPyV was 59.6% and of TSPyV, 67.3%. 

Conclusions: MCPyV DNA, unlike TSPyV DNA, occurs in low copy number in serum samples from a notable proportion of aging individuals.

Whether this reflects enhanced viral replication possibly due to waning immune surveillance, and is associated with increased MCC risk, deserves exploration.

Author: Mohammadreza SadeghiMatti AronenTingting ChenLaura JarttiTuomas JarttiOlli RuuskanenMaria Söderlund-VenermoKlaus Hedman
Credits/Source: BMC Infectious Diseases 2012, 12:383

7th Space

Metastatic Merkel cell carcinoma of the oral cavity in a human immunodeficiency virus-positive patient and the detection of Merkel cell polyomavirus

Dec 2011

Li M, Saghafi N, Freymiller E, Basile JR, Lin YL.

Source

Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, California.

Abstract

The etiology of Merkel cell carcinoma (MCC) was recently linked to a newly identified human virus, the Merkel cellpolyomavirus (MCPyV). The discovery that MCPyV plays an important role in the tumorigenesis of >80% of MCCs provides an explanation for the increased incidence of this rare malignancy in human immunodeficiency virus (HIV)-positive and immunocompromised patients. We report an unusual metastasis of MCC to the mandibular gingiva of an HIV-positive patient. In addition to routine hematoxylin-eosin and immunohistochemical studies, we also performed a molecular biologic analysis to look for the presence of MCPyV in this case. We detected evidence of the MCPyV genome in this lesion similar to what has been observed for MCCs reported in other immunocompromised patients. These results stress the importance of combining morphologic and molecular biologic analyses in the evaluation of MCC, because confirmation of viral etiology would likely affect the choice of treatment and prognosis when specific antiviral therapy becomes available for this aggressive tumor

Science Direct.

Merkel cell polyomavirus: A newly discovered human virus with oncogenic potential.

Jan 2013

Spurgeon ME, Lambert PF.

Source

Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1400 University Ave. Madison, WI 53706, USA.

Abstract

Keywords:

• DNA tumor virus; 
• Merkel; 
• Tumor antigen; 
• Merkel cell polyomavirus; 
• MCV; 
• MCPyV; 
• Polyomavirus; 
• Merkel cell carcinoma

A marked escalation in the rate of discovery of new types of human polyomavirus has occurred over the last five years largely owing to recent technological advances in their detection. Among the newly discovered viruses, Merkel Cell Polyomavirus (MCPyV or MCV) has gained the most attention due to its link with a rare human cancer. Infection with MCPyV is common in the human population, and the virus is detected in several anatomical locations, but most frequently in skin. Study of MCPyV molecular virology has been complicated by the lack of straightforward cell culture models, but recent in vitro studies are making strides towards understanding the virus life cycle, its cellular tropism, and mode of transmission. While MCPyV shares several traditional traits with other human polyomaviruses, the burst of research since its discovery reveals insight into a virus with many unique genetic and mechanistic features. The evidence for a causal link between MCPyV and the rare neuroendocrine cancer, Merkel Cell Carcinoma (MCC), is compelling. A majority of MCCs contain clonally integrated viral DNA, express viral T antigen transcripts and protein, and exhibit an addiction to the viral large T and small t antigen oncoproteins. The MCPyV large T antigen contains MCC tumor-specific mutations that ablate its replication capacity but preserve its oncogenic functions, and the small t antigen promotes an environment favorable for cap-dependent translation. The mechanisms of MCPyV-induced transformation have not been fully elucidated, but the likely etiological role of this new polyomavirus in human cancer provides a strong opportunity to expand knowledge of virus-host interactions and viral oncology.

Elsevier - Scielo

Merkel cell carcinoma.

Dec 2012

Han SY, North JP, Canavan T, Kim N, Yu SS.

Source

Department of Dermatology, University of California, San Francisco, 1701 Divisadero Street, 3rd Floor, San Francisco, CA 94115, USA.

Abstract

Merkel cell carcinoma (MCC) is a rare but aggressive carcinoma of the skin, arising most commonly in sun-exposed sites of elderly patients. The diagnosis is based on characteristic histopathologic features. In 2008, the discovery of the Merkel cell polyomavirus led to intensified research into the viral pathogenesisis of MCC. MCC staging guidelines were established in 2010, and it demonstrated the importance of distinguishing clinical vs. pathologic evaluation of lymph nodes in MCC. Surgery and/or radiation is of the mainstay of therapy for early disease, while chemotherapy is reserved for more advanced disease. Treatments based on immunologic mechanisms are currently in development.

SciVerse

Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus.

Nov 2012

Rodig SJ, Cheng J, Wardzala J, Dorosario A, Scanlon JJ, Laga AC, Martinez-Fernandez A, Barletta JA, Bellizzi AM,Sadasivam S, Holloway DT, Cooper DJ, Kupper TS, Wang LC, Decaprio JA.

Abstract

A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T antigen by immunohistochemistry. In addition, we expanded the repertoire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique MCC tumors tested. We also detected inactivating point substitution mutations of TP53 in the two MCC specimens that lacked large T antigen expression and in only 1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen.

PubMed

Immunohistochemical prognostication of Merkel cell carcinoma: p63 expression but not polyomavirus status correlates with outcome.

July 2012

Hall BJ, Pincus LB, Yu SS, Oh DH, Wilson AR, McCalmont TH.

Source

Department of Pathology, University of Utah, Salt Lake City, UT, USA.

Abstract

Merkel cell carcinoma (MCC) represents a cutaneous malignancy with high associated mortality. Numerous studies have attempted to define characteristics to more accurately predict outcome. Two recent studies have demonstrated that Merkelcell polyomavirus (MCPyV) seropositivity correlated with a better prognosis, while a third study revealed no difference. Expression of p63 by tumor cell nuclei has been shown to be associated with a worse prognosis in a European cohort. To better understand the relationship between prognosis and MCPyV or p63 status, we used immunohistochemistry to evaluate both attributes in 36 US patients with MCC. Our results show that when considered as a binary variable, p63 expression represents a strong risk factor (p < 0.0001, hazards ratio (HR) = ∞) for shortened survival. In addition, our results show that MCPyV status does not correlate with survival (p = 0.6067, HR = 1.27). Our study corroborates the European observation that p63 immunoexpression is useful as a prognostic tool. Larger studies will need to be performed in order to determine whether p63 status should be included in MCC staging, since our study is limited by its relative small size.

Wiley OnLine

Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas.

Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas.

Br J Dermatol. 2009 May

Varga E, Kiss M, Szabó K, Kemény L.
Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, H-6720 Szeged, Hungary.

Background Merkel cell carcinoma (MCC) is a rare, aggressive tumour for which an increasing incidence has been reported. A new human polyomavirus, Merkel cell polyomavirus (MCV), was recently isolated from these tumours by applying digital transcriptome subtraction methodology. Objectives To detect the presence or absence of MCV in MCCs and other, randomly selected neoplasms. Methods Nine primary or recurrent MCCs from seven patients were examined; 29 other tumours (squamous cell, basal cell and basosquamous carcinomas and malignant melanomas) were examined for comparative purposes. Viral large T protein (LT1 and LT3), and viral capsid protein (VP1) were detected by primer-directed amplification, using a polymerase chain reaction (PCR)-based method, and the amplified PCR products were analysed by agarose gel electrophoresis and subsequent sequence analysis. Results The presence of viral T antigen and/or viral capsid DNA sequences was demonstrated in seven of the eight MCC lesions. None of the comparative samples contained MCV DNA. Conclusions Our findings strongly support the hypothesis that MCV infection may well be specific for MCC, and MCV may play a role in the pathogenesis of MCC.

WileyInterScience