Jérôme T. J. Nicol

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

ABSTRACT Six new human polyomaviruses have been identified since 2008 (Merkel cell polyomavirus [MCPyV], human polyomavirus 6 [HPyV6], HPyV7, HPyV9, trichodysplasia spinulosa polyomavirus [TSPyV], and Malawi polyomavirus [MWPyV]). The presence of specific antibodies against MCPyV, HPyV6, HPyV7, HPyV9, and TSPyV in 828 Italian subjects aged 1 to 100 years was investigated by virus-like particle-based enzyme-linked immunosorbent assays (ELISAs). The findings indicate that all of these new polyomaviruses circulate widely in humans, with seroprevalences in adulthood ranging from 39.4% for HPyV9 to 87.1% for MCPyV, and that primary exposure is most intense in childhood, with the exception of HPyV7 and HPyV9, for which the seroprevalence increased throughout life. The proportion of subjects with high antibody titers was found to increase with age for MCPyV and to decrease with age for TSPyV.

Human Merkel cell polyomavirus: virological background and clinical implications

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.

Seroprevalence and Cross-reactivity of Human Polyomavirus 9

Many humans have antibodies against simian lymphotropic polyomavirus (LPyV), but its DNA has not been found in humans. Identification of human polyomavirus 9 (HPyV9) led us to compare the seroprevalence and cross-reactivity of LPyV and HpyV9. Results could indicate that humans who have antibodies against LPyV are infected by HPyV9.

Seroprevalence of Human Malawi Polyomavirus

ABSTRACT The seroprevalence of the recently discovered human Malawi polyomavirus (MWPyV) was determined by virus-like particle-based 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.

Molecular Epidemiology of Merkel Cell Polyomavirus: Evidence for Geographically Related Variant Genotypes

ABSTRACT Merkel cell polyomavirus (MCPyV) is linked to a cutaneous cancer mainly occurring in Caucasians. DNA from skin swabs of 255 adults, originating from the 5 continents, were subjected to MCPyV PCRs. Phylogenetic analyses demonstrate the existence of 5 major geographically related MCPyV genotypes (Europe/North America, Africa [sub-Saharan], Oceania, South America, and Asia/Japan).

Identification of the Neutralizing Epitopes of Merkel Cell Polyomavirus Major Capsid Protein within the BC and EF Surface Loops

Merkel cell polyomavirus (MCPyV) is the first polyomavirus clearly associated with a human cancer, i.e. the Merkel cell carcinoma (MCC). Polyomaviruses are small naked DNA viruses that induce a robust polyclonal antibody response against the major capsid protein (VP1). However, the polyomavirus VP1 capsid protein epitopes have not been identified to date. The aim of this study was to identify the neutralizing epitopes of the MCPyV capsid. For this goal, four VP1 mutants were generated by insertional mutagenesis in the BC, DE, EF and HI loops between amino acids 88-89, 150-151, 189-190, and 296-297, respectively. The reactivity of these mutants and wild-type VLPs was then investigated with anti-VP1 monoclonal antibodies and anti-MCPyV positive human sera. The findings together suggest that immunodominant conformational neutralizing epitopes are present at the surface of the MCPyV VLPs and are clustered within BC and EF loops.

Merkel Cell Polyomavirus in Merkel Cell Carcinoma: Clinical and Therapeutic Perspectives

Merkel cell carcinoma (MCC) is a rare and often aggressive cutaneous cancer with a poor prognosis. The incidence of this cancer increases with age, immunodeficiency and sun exposure. Merkel cell polyomavirus (MCPyV), a new human polyomavirus identified in 2008, is detected in the majority of the MCCs and there is a growing body of evidence that healthy human skin harbors resident or transient MCPyV. A causal link between MCPyV and MCC has been evidenced and this is the first polyomavirus to be clearly implicated as a causal agent underlying a human cancer, and MCPyV was recently classified as a 2A carcinogen. MCC is thus a rare tumor caused by a very common viral skin infection. The aim of this review is to provide a basic overview of the epidemiological, clinical, and pathological characteristics of MCC, to present the current knowledge on MCPyV polyomavirus and its causal association with MCC development, and to describe the therapeutic implications of this causal link.

Serological Cross-Reactivity between Merkel Cell Polyomavirus and Two Closely Related Chimpanzee Polyomaviruses

Phylogenetic analyses based on the major capsid protein sequence indicate that Merkel cell polyomavirus (MCPyV) and chimpanzee polyomaviruses (PtvPyV1, PtvPyV2), and similarly Trichodysplasia spinulosa-associated polyomavirus (TSPyV) and the orangutan polyomavirus (OraPyV1) are closely related. The existence of cross-reactivity between these polyomaviruses was therefore investigated. The findings indicated serological identity between the two chimpanzee polyomaviruses investigated and a high level of cross-reactivity with Merkel cell polyomavirus. In contrast, cross-reactivity was not observed between TSPyV and OraPyV1. Furthermore, specific antibodies to chimpanzee polyomaviruses were detected in chimpanzee sera by pre-incubation of sera with the different antigens, but not in human sera.

Age-specific seroprevalence of human polyomavirus 12 and Saint Louis and New Jersey polyomaviruses

The presence of specific antibodies against human polyomavirus 12, Saint Louis polyomavirus and New Jersey polyomavirus was investigated by using virus-like particle-based ELISAs with serum samples from 706 Italians aged 1- to 100-years-old. The findings indicate that these polyomaviruses circulate widely in humans, with peak seroprevalence, observed at adulthood, of 97.3%, 93.3%, 57.5%, for human polyomavirus 12, Saint Louis polyomavirus and New Jersey polyomavirus, respectively.