Seroprevalence of human Malawi polyomavirus.

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.

Anogenital distribution of mucosal HPV in males and females before and after renal transplantation.

INTRODUCTION: Immunosuppressive drugs taken by transplant recipients may favor HPV infection at anogenital sites. HPV-type prevalence was studied in males and females before and after renal transplantation. PATIENTS AND METHODS: Anal, cervical and penile samples were taken from 62 patients before transplantation and from 41 patients after transplantation. HPV DNA was investigated using the INNO-LiPA HPV genotyping extra test and HPV-type distribution determined. RESULTS: Before transplantation, up to 30% of analyzed samples harbored HPV DNA, with the highest prevalence found in cervical specimens (60%). After transplantation, a trend toward HPV clearance was observed in females. By contrast, a trend toward incident infections by a wide variety of HPV genotypes at the penis and anal level was documented in men. CONCLUSION: High prevalence of HPV at anogenital sites was documented before and after renal transplantation. Immunosuppressive drugs taken after transplantation may impact HPV acquisition or reactivation, especially in males. Special attention should be paid in view of preventing HPV-associated diseases in this vulnerable population.

Serum antibodies against mimotopes of Merkel cell polyomavirus oncoproteins detected by a novel immunoassay in healthy individuals and Merkel cell carcinoma patients.

Merkel cell polyomavirus (MCPyV) is the foremost causative factor of Merkel cell carcinoma (MCC), a rare yet highly aggressive skin cancer. Although the evaluation of circulating IgG antibodies against Merkel cell polyomavirus (MCPyV) LT/sT oncoproteins is clinically useful for MCC diagnosis/prognosis, a limited number of assays for identifying such antibodies have been developed. Herein, a novel indirect immunoassay with synthetic epitopes/mimotopes of MCPyV oncoproteins was computationally designed and experimentally validated on control sera and sera from healthy individuals and MCC patients. Upon computational design of five synthetic peptides, the performance of the immunoassay in detecting anti-oncoprotein IgGs in MCPyV-positive and -negative control sera was evaluated. The immunoassay was afterwards extended on sera from healthy individuals, and, for longitudinal analysis, MCC patients. Performance properties such as sensitivity and specificity and positive/negative predictive values were adequate. Receiver-operating characteristic (ROC) curves indicated that the areas under the curves (AUCs) were within the low/moderately accurate ranges. Immunoassay was repeatable, reproducible and accurate. As expected, the serum anti-oncoprotein IgG prevalence in healthy individuals was low (2%-5%). Anti-oncoprotein IgGs slightly increased when MCC patients experienced partial tumour remission and/or stable disease, compared to baseline. Our data indicate that the newly developed immunoassay is reliable for detecting circulating anti-oncoprotein IgGs both in healthy individuals and MCC patients.

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.

Generation of Merkel cell polyomavirus (MCV)-like particles and their application to detection of MCV antibodies.

The genome of a new human polyomavirus, known as Merkel cell polyomavirus (MCV), has recently been reported to be integrated within the cellular DNA of Merkel cell carcinoma (MCC), a rare human skin cancer. To investigate MCV seroprevalence in the general population, we expressed three different MCV VP1 in insect cells using recombinant baculoviruses. Viruslike particles (VLPs) were obtained with only one of the three VP1 genes. High-titer antibodies against VP1 VLPs were detected in mice immunized with MCV VLPs, and limited cross-reactivity was observed with BK polyomavirus (BKV) and lymphotropic polyomavirus (LPV). MCV antibodies were detected in 77% of the general population, with no variations according to age.

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.

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.

Antibodies to VP1 of swine pasivirus in humans without evidence of transmission from a pig source.

BACKGROUND: Swine pasivirus (SPaV1) is a recently described enteric virus close to human parechoviruses and highly prevalent in pigs. Antibodies to Escherichia coli-expressed VP1 of SpaV1 have been found in a majority of humans in China. OBJECTIVES: The objectives were to estimate the antibody prevalence in a European country, to test if exposure to the virus was linked to pig products and if this exposure was a risk factor for the development of diabetes type 1. STUDY DESIGN: An ELISA test was developed and used to screen 842 healthy subjects with known exposure to pig products, 39 patients with diabetes type 1 and 20 controls. RESULTS: We identified a high seroprevalence (15.6%) reacting to VP1 of SPaV1 among healthy human subjects. Analysis of risk factors argues against cross-species transmission from pigs as the source of infection. Data also indicate that the presence of SPaV1 VP1-binding antibodies is not associated with diabetes type 1 in humans. CONCLUSION: Our results suggest that the seroreactivity frequently found in humans against SpaV1 is due to cross-reactivity with related antigen, perhaps a picornavirus, and that SpaV1 is not a zoonotic virus.

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.

Anti-HPV16 E2 protein T-cell responses and viral control in women with usual vulvar intraepithelial neoplasia and their healthy partners.

T-cell responses (proliferation, intracellular cytokine synthesis and IFNγ ELISPOT) against human papillomavirus 16 (HPV16) E2 peptides were tested during 18 months in a longitudinal study in eight women presenting with HPV16-related usual vulvar intraepithelial neoplasia (VIN) and their healthy male partners. In six women, anti-E2 proliferative responses and cytokine production (single IFNγ and/or dual IFNγ/IL2 and/or single IL2) by CD4+ T lymphocytes became detectable after treating and healing of the usual VIN. In the women presenting with persistent lesions despite therapy, no proliferation was observed. Anti-E2 proliferative responses were also observed with dual IFNγ/IL2 production by CD4+ T-cells in six male partners who did not exhibit any genital HPV-related diseases. Ex vivo IFNγ ELISPOT showed numerous effector T-cells producing IFNγ after stimulation by a dominant E2 peptide in all men and women. Since the E2 protein is absent from the viral particles but is required for viral DNA replication, these results suggest a recent infection with replicative HPV16 in male partners. The presence of polyfunctional anti-E2 T-cell responses in the blood of asymptomatic men unambiguously establishes HPV infection even without detectable lesions. These results, despite the small size of the studied group, provide an argument in favor of prophylactic HPV vaccination of young men in order to prevent HPV16 infection and viral transmission from men to women.

High levels of antibodies against merkel cell polyomavirus identify a subset of patients with merkel cell carcinoma with better clinical outcome.

PURPOSE: A new human polyomavirus, Merkel cell polyomavirus (MCV), was identified in 2008 in tumor tissue of patients with Merkel cell carcinoma (MCC), a relatively rare human skin cancer. In this study, we investigated patients with MCC and controls for the presence of antibodies against MCV and their association with clinical characteristics. PATIENTS AND METHODS: Antibodies against MCV were investigated by enzyme-linked immunosorbent assay in 68 patients with MCC and 82 controls using VP1 virus-like particles produced in insect cells. RESULTS: Antibodies against MCV were detected in all patients with MCC and in 85% of controls. However, high antibody titers (> 10,000) were rarely observed in controls (7.3%) and they were detected in 64.7% of patients with MCC (P < .001) in contrast to the absence of VP1 expression in tumor samples. In addition, the geometric mean titer of anti-MCV in patients with MCC was around 14 times higher than that observed in MCV-positive controls (P < .001) and was not correlated with tumor viral load. High antibody titers were not found to be associated with any subject or tumor characteristics, but better progression-free survival was observed in patients with high antibody titers (hazard ratio, 4.6; 95% CI, 1.7 to 12.2; P = .002). CONCLUSION: High titers of MCV antibodies in a much higher proportion of patients with MCC than in controls confirmed the association between MCV infection and MCC. The findings also indicated that a better progression-free survival occurred in patients with high MCV antibody titers and suggested that there are at least two distinct etiologic causes of MCC.