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.
Introduction. Naturally-occurring variants of Human papillomavirus (HPV) genotypes have been defined as lineages and sub-lineages, but little is known about the impact of this diversity on protein function. We have previously demonstrated that variation within the major (L1) and minor (L2) capsid proteins impact the susceptibility of HPV to serum antibodies elicited by vaccination and natural infection. Higher resolution mapping of variant residues, however, requires the availability of appropriate tools, such as type-specific monoclonal antibodies (MAbs). These empirical data will improve our understanding of the consequences of natural variation on capsid antigenicity. Methods. We investigated the susceptibility of 37 representative pseudovirus variants of HPV16, HPV18, HPV31, HPV33, HPV45, HPV52 and HPV58 to neutralization by type-specific murine MAbs raised against the A lineage of their respective genotypes. Homology models derived from available HPV L1 crystal structures were generated to permit mapping of variant residues onto the surface-exposed L1 protein for relevant variants Results. Type-specific lineage A-specific MAbs demonstrated differential reactivity against some, but not all, variants within its respective genotype. Some of these differences were minor (<4 fold) while some variants displayed orders of magnitude reduced sensitivity. These differences in antigenicity were mapped to a limited number of variant residues on the capsid surface. Conclusions. These data contribute to our understanding of HPV L1 variant antigenicity and may have implications for seroprevalence or vaccine immunity studies based upon L1 antigens.
ABSTRACT The first genome of one species of the Scedosporium apiospermum complex, responsible for localized to severe disseminated infections according to the immune status of the host, will contribute to a better understanding of the pathogenicity of these fungi and also to the discovery of the mechanisms underlying their low susceptibility to current antifungals.
