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.

Fig. 1.

Histograms of seroreactivities to JCPyV (JCV) (A), BKPyV (BKV) (B), and MCPyV (MPV) (C) VP1 virus-like particles of samples from 42 children less than 10 years of age. The density is the number of serum samples on a continuous scale.

Fig. 2.

SDS-PAGE analysis of Merkel cell polyomavirus, BK virus, and JC virus VP1 virus-like particles. Five-microgram samples of gradient-purified MCPyV (MC), BKPyV (BK), or JCPyV (JC) VP1 virus-like particles produced in insect cells from recombinant baculoviruses were subjected to SDS-PAGE. Molecular weight markers (MW) are shown in lane 1, with the sizes of markers (10³) indicated to the left of the gel.

Fig. 3.

Electron micrograph of MCPyV VP1 virus-like particles at a magnification of ×105,000. The bar corresponds to 100 nm.

Fig. 4.

Age-specific seroprevalence of Merkel cell polyomavirus, BK virus, and JC virus among 945 individuals recruited from hospital-based general and subspecialty outpatient clinics. Serum samples were tested at a 1:200 dilution in VLP-based ELISAs. The distribution of reactivities of serum samples from children less than 10 years of age was used to set cutoff points for seropositivity, and results are displayed as the percent positive in 10-year age groups. Numbers used to construct the graph are shown in Table 1.