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.

Structures of Merkel Cell Polyomavirus VP1 Complexes Define a Sialic Acid Binding Site Required for Infection.

July 2012

Neu U, Hengel H, Blaum BS, Schowalter RM, Macejak D, Gilbert M, Wakarchuk WW, Imamura A, Ando H, Kiso M, Arnberg N, Garcea RL, Peters T, Buck CB, Stehle T.

Source

Interfaculty Institute of Biochemistry, University of Tuebingen, Tuebingen, Germany.

Abstract

The recently discovered human Merkel cell polyomavirus (MCPyV or MCV) causes the aggressive Merkel cell carcinoma(MCC) in the skin of immunocompromised individuals. Conflicting reports suggest that cellular glycans containing sialic acid (Neu5Ac) may play a role in MCPyV infectious entry. To address this question, we solved X-ray structures of the MCPyV major capsid protein VP1 both alone and in complex with several sialylated oligosaccharides. A shallow binding site on the apical surface of the VP1 capsomer recognizes the disaccharide Neu5Ac-α2,3-Gal through a complex network of interactions. MCPyV engages Neu5Ac in an orientation and with contacts that differ markedly from those observed in other polyomavirus complexes with sialylated receptors. Mutations in the Neu5Ac binding site abolish MCPyV infection, highlighting the relevance of the Neu5Ac interaction for MCPyV entry. Our study thus provides a powerful platform for the development of MCPyV-specific vaccines and antivirals. Interestingly, engagement of sialic acid does not interfere with initial attachment of MCPyV to cells, consistent with a previous proposal that attachment is mediated by a class of non-sialylated carbohydrates called glycosaminoglycans. Our results therefore suggest a model in which sialylated glycans serve as secondary, post-attachment co-receptors during MCPyV infectious entry. Since cell-surface glycans typically serve as primary attachment receptors for many viruses, we identify here a new role for glycans in mediating, and perhaps even modulating, post-attachment entry processes.

Full text article:

PLOS/Pathogens

Merkel Cell Carcinoma Concurrent with Bowen's Disease.

Feb 2012

Park HC, Kang HS, Park KT, Oh YH, Yu HJ, Kim JS.

Source

Department of Dermatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.

Abstract

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy of the elderly and immunocompromised patients. It is occasionally found coexisting with other diseases, such as squamous cell carcinoma, basal cell carcinoma, actinic keratosis, miscellaneous adnexal tumors, and rarely Bowen disease. A 75-year-old woman presented with a 6-month history of an irregularly shaped erythematous patch on the left mandibular angle. Three months later, a 1.5×1.0 cm sized painless and rapidly growing erythematous nodule developed on the patch. Microscopically, the patch lesion was consistent with that of Bowen disease. The nodular lesion showed a number of small uniform hyperchromatic cells with scanty cytoplasm. It showed dense small-cell like nodular infiltration in the dermis. Immunohistochemical staining for cytokeratin 20 showed a positive result with a dot-like perinuclear pattern. Additionally, the result for thyroid transcription factor-1 was negative, which is positive in small cell neuroendocrine carcinoma. From these findings, we diagnosed this lesion as MCC concurrent with Bowen disease.

Annals of Dermatology