Age-Specific Seroprevalence of Merkel Cell Polyomavirus, BK Virus, and JC Virus

Abstract

We produced capsids of Merkel cell polyomavirus (MCPyV) in a baculovirus expression system and developed a virus-like particle (VLP) enzyme-linked immunosorbent assay (ELISA). To determine age-specific seroprevalence, serum samples were collected from 947 individuals attending hospital outpatient clinics and ranging in age from 1 to 93 years. To evaluate the association between exposure to MCPyV and Merkel cell cancer (MCC), plasma samples were obtained from 33 MCC patients and 37 controls. MCPyV seroprevalence was 45% in children under 10 years of age, increased to 60% in the next decade of life, and peaked at 81% among those 60 to 69 years of age. Levels of MCPyV capsid antibodies were positively correlated with age (P ‫؍‬ 0.007). Virus specificity of MCPyV seroreactivity was supported by competitive inhibition of reactivity by MCPyV VLPs and not by BK polyomavirus (BKPyV) VLPs. MCPyV seroprevalence was greater among MCC patients (91%) than controls (68%; age-adjusted P value, 0.32); the mean level of MCPyV antibodies was also greater (P ‫؍‬ 0.04). The age-specific seroprevalence of MCPyV shares with previously known polyomaviruses, BKPyV and JC polyomavirus (JCPyV), evidence of widespread exposure in human populations beginning early in life. MCPyV age-specific seroprevalence also has unique features. Seroprevalence among children is higher than that of JCPyV but lower than that of BKPyV. Among older adults, MCPyV seroprevalence remains high, while that of BKPyV declines and that of JCPyV continues to rise. In agreement with results from other studies, we found an association between MCPyV seropositivity and MCC, and higher levels of serum MCPyV capsid antibodies in MCC patients than in controls.Merkel cell polyomavirus (MCPyV), a new human polyomavirus, was recently discovered by molecular techniques in Merkel cell carcinoma (MCC) (11), a rare and aggressive skin tumor (20,22). Studies from North America and Europe have detected MCPyV DNA by PCR in 69 to 100% of MCC tumors (1,9,11,13,14,17,25). The virus has also been detected in rare instances and in low copy numbers in cutaneous, gastrointestinal, and respiratory tract samples from healthy individuals (2,11,15). Little is known about the natural history of MCPyV infection in human populations. Serological assays can reveal the extent of past exposure to a virus and provide insights into its epidemiology. We and others have developed virus-like particle (VLP)-based enzyme-linked immunosorbent assays (ELISAs) to measure antibodies to various human and animal polyomaviruses (10, 27, 31). Polyomavirus VLPs are empty viral capsids produced by expression of the gene for the major capsid protein, VP1, in a eukaryotic expression system. VLPs resemble native virions morphologically and retain their immunological properties, including the ability to bind antiviral capsid antibodies. We now report the development of a VLP-based ELISA to detect antibodies to MCPyV and its application for comparison of the age-specific seroprevalence of MCPyV to those of two other huma...

Human Merkel cell polyomavirus: virological background and clinical implications

“…The mean viral load has been reported to be 1-5 copies per cell, in agreement with integration of the viral genome into chromosomal DNA (1,90,93,94). Anti-VP1 antibodies have been detected in 88-100% of MCC cases (7,8,14,25). In addition, the capsid antibody titer in many of these MCC cases is much higher than observed in control populations.…”

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

“…When expressed in mammalian or insect cells, VP1 proteins (or VP1 + VP2 proteins) self-assemble into 45-55 nm diameter virus-like particles (VLPs) (Fig. 2) that are used in serological assays (7,(12)(13)(14).…”

The use of mathematical and computational models to define the role of mutation and infection in colorectal cancer.

“…The parameters frequency-of-infection-year years and probability-of-JCV-spreadingto-neighbor were calibrated so that the modeled incidence of infection had a pattern similar to that observed in Viscidi et al [144], Knowles et al [68].…”

“…Given that transit cells are rapidly sloughed off, it is frequently argued that colon crypt stem cells accumulate the mutations necessary to convert them into cancer JCV is a very common DNA virus, occurring in 45%-80.5% of adults [144,18].…”