Age-Specific Seroprevalences of Merkel Cell Polyomavirus, Human Polyomaviruses 6, 7, and 9, and Trichodysplasia Spinulosa-Associated Polyomavirus

Nicol, Jérôme; Robinot, Rémy; Carpentier, A.; Carandina, Giovanni; Mazzoni, Elisa; Tognon, Mauro; Touzé, Antoine; Coursaget, Pierre

doi:10.1128/cvi.00438-12

Cited by 135 publications

(206 citation statements)

References 22 publications

(36 reference statements)

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…Then, MCPyV sequences were detected in MCC in up to 80% of cases, whereas Ig antibodies against MCPyV were revealed in approximately 80% of healthy subjects and MCC-affected patients. These results indicate that MCPyV, which is potentially oncogenic, is a ubiquitous human virus (9).…”

Section: Introductionmentioning

confidence: 80%

Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF

Rotondo

Bononi

Puozzo

et al. 2017

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arisen in patients affected by autoimmune diseases and treated with biologic drugs.Experimental Design: Serum samples from patients with MCC were analyzed for the presence and titer of antibodies against antigens of the oncogenic Merkel cell polyomavirus (MCPyV). IgG antibodies against the viral oncoproteins large T (LT) and small T (ST) antigens and the viral capsid protein-1 were analyzed by indirect ELISA. Viral antigens were recombinant LT/ST and viruslike particles (VLP), respectively. MCPyV DNA sequences were studied using PCR methods in MCC tissues and in peripheral blood mononuclear cells (PBMC). Immunohistochemical (IHC) analyses were carried out in MCC tissues to reveal MCPyV LT oncoprotein.Results: MCPyV DNA sequences identified in MCC tissues showed 100% homology with the European MKL-1 strain.PBMCs from patients tested MCPyV-negative. Viral DNA loads in the three MCC tissues were in the 0.1 to 30 copy/cell range. IgG antibodies against LT/ST were detected in patients 1 and 3, whereas patient 2 did not react to the MCPyV LT/ST antigen. Sera from the three patients with MCC contained IgG antibodies against MCPyV VP1. MCC tissues tested MCPyV LT-antigenpositive in IHC assays, with strong LT expression with diffuse nuclear localization. Normal tissues tested MCPyV LT-negative when employed as control.Conclusions: We investigated three new MCCs in patients affected by rheumatologic diseases treated with biologic drugs, including TNF. A possible cause-effect relationship between pharmacologic immunosuppressive treatment and MCC onset is suggested. Indeed, MCC is associated with MCPyV LT oncoprotein activity.

show abstract

Section: Introductionmentioning

confidence: 80%

Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF

Rotondo

Bononi

Puozzo

et al. 2017

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 90%

“…This seroprevalence was similar to the seroprevalence of 39.4% reported for HPyV9 (12) but lower than the seroprevalence reported for MCPyV, HPyV6, HPyV7, and TSPyV (63.6% to 87.0%) (12). The relatively low seroprevalence observed for MWPyV correlates with the detection of its DNA in only 2.3% of human stools (2), similar to levels observed for HPyV9, for which seroprevalence and DNA prevalence are low (12,15,16).MWPyV seroconversion occurs early in life, as observed with other polyomaviruses (8, 12), since 26.9% of 1-to 2-year-old children were seropositive, followed by a seroprevalence peak of 68.2% in 2-to 4-year-old children.The OD value at a 1:100 dilution of the sera can be used as a surrogate for antibody titer, and it has been shown that titers increase with age for MCPyV and decrease with age for TSPyV (12). A decrease in the percentage of high reactivity with age was also observed for MWPyV, suggesting that MWPyV clearance occurs or that there is an absence of reactivation with age, as reported for TSPyV (12).…”

mentioning

confidence: 91%

See 1 more Smart Citation

Seroprevalence of Human Malawi Polyomavirus

et al. 2014

Self Cite

View full text Add to dashboard Cite

The seroprevalence of the recently discovered human Malawi polyomavirus (MWPyV) was determined by virus-like particlebased enzyme-linked immunosorbent assay (ELISA) in age-stratified Italian subjects. The findings indicated that MWPyV infection occurs early in life, and seroprevalence was shown to reach 42% in adulthood.T welve human polyomaviruses have been described to date, including JC and BK polyomaviruses (JCPyV and BKPyV), Karolinska Institute polyomavirus (KIPyV), Washington University polyomavirus (WUPyV), Merkel cell polyomavirus (MCPyV), human polyomaviruses 6 and 7 (HPyV6 and HPyV7), trichodysplasia spinulosa-associated polyomavirus (TSPyV), human polyomavirus 9 (HPyV9) (1), and three recently identified polyomaviruses, i.e., Malawi polyomavirus/human polyomavirus 10 (MWPyV/HPyV10), Saint Louis polyomavirus (STLPyV) isolated from stools (2-4), and human polyomavirus 12 (HPyV12) identified in the liver (5).Polyomavirus infections are ubiquitous, with seroprevalence ranging from 40 to 90% in adults, and asymptomatic infections occur early in childhood (6-12).Four human polyomaviruses are associated with disease. JCPyV causes progressive multifocal leukoencephalopathy, BKPyV is the cause of hemorrhagic cystitis in allogeneic hematopoietic stem cell transplant patients and induced nephropathy frequently followed by graft loss in renal transplant patients. MCPyV is responsible for Merkel cell carcinoma (MCC), which occurs mainly in elderly individuals and immunocompromised subjects, and TSPyV is associated with trichodysplasia spinulosa. JCPyV-, BKPyV-, and TSPyV-associated diseases have been observed only in immunocompromised subjects (1,13).In this study, we investigated the seroepidemiology of the recently identified Malawi polyomavirus in an Italian population using a virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA) and evaluated the existence of crossreactivity with MCPyV, HPyV6, HPyV7, TSPyV, and HPyV9 polyomaviruses.MWPyV seroprevalence was determined in 825 Italian subjects 1 to 100 years of age. This study population has previously been investigated for reactivity against five other polyomaviruses (12), and the approach here was similar. Antibodies against MWPyV were determined using a VLP-based ELISA (14). The MWPyV VP1 coding sequence (GenBank accession no. NC_018102.1) was codon optimized for expression in Spodoptera frugiperda cells (Genscript, Piscataway, NJ) and used to generate a recombinant baculovirus. The presence of 45-to 50-nm VLPs and smaller particles was observed by electron microscopy (Fig. 1). Purified MWPyV VLPs (100 ng/well in phosphate-buffered saline [PBS]) were used to sensitize microplates (Maxisorp; Nunc) overnight at 4°C. Briefly, sera were diluted 1:100, and peroxidase-conjugated anti-human IgG (Southern Biotech, Clinisciences, Nanterre, France) diluted 1:20,000 was used to detect human IgG binding (14). A histogram of the ELISA optical density (OD) values in 1-to 10-year-old children (data not shown) revealed a bimodal distribution of seroreacti...

show abstract

“…Seroprevalence of 50-95% is reported in adults (7,(12)(13)(14)(25)(26)(27)(28)(29). The age-specific seroprevalence of MCPyV (Fig.…”

Section: Serologymentioning

confidence: 99%

Human Merkel cell polyomavirus: virological background and clinical implications

Coursaget

Samimi

Nicol

et al. 2013

APMIS

Self Cite

View full text Add to dashboard Cite

The Merkel cell polyomavirus (MCPyV), identified in humans in 2008, is associated with a relatively rare but aggressive neuroendocrine skin cancer, the Merkel cell carcinoma (MCC). MCC incidence is increasing due to the advancing age of the population, the increase in damaging sun exposure and in the number of immunocompromised individuals. MCPyV must be considered as the etiological agent of MCC and thus is the first example of a human oncogenic polyomavirus. MCPyV infection is common, and seroprevalence studies indicate that widespread exposure begins early in life. The majority of adults have anti-MCPyV antibodies and there is a growing body of evidence that healthy human skin harbors resident or transient MCPyV suggesting that MCPyV infection persists throughout life. However, the mode of transmission, the host cells, and the latency characteristics of this virus remain to be elucidated. In addition, it is still not clear whether MCPyV is associated with diseases or lesions other than Merkel cell carcinoma. The etiologic role of MCPyV in MCC opens up opportunities to improve the understanding of this cancer and to potentially improve its treatment.

show abstract

Age-Specific Seroprevalences of Merkel Cell Polyomavirus, Human Polyomaviruses 6, 7, and 9, and Trichodysplasia Spinulosa-Associated Polyomavirus

Cited by 135 publications

References 22 publications

Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF

Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF

Seroprevalence of Human Malawi Polyomavirus

Human Merkel cell polyomavirus: virological background and clinical implications

Contact Info

Product

Resources

About