Seroepidemiology of human polyomaviruses

Abstract

In addition to the previously characterized viruses BK and JC, three new human polyomaviruses (Pys) have been recently identified: KIV, WUV, and Merkel Cell Py (MCV). Using an ELISA employing recombinant VP1 capsid proteins, we have determined the seroprevalence of KIV, WUV, and MCV, along with BKV and JCV, and the monkey viruses SV40 and LPV. Soluble VP1 proteins were used to assess crossreactivity between viruses. We found the seroprevalence (+/- 1%) in healthy adult blood donors (1501) was SV40 (9%), BKV (82%), JCV (39%), LPV (15%), KIV (55%), WUV (69%), MCV strain 350 (25%), and MCV strain 339 (42%). Competition assays detected no sero-crossreactivity between the VP1 proteins of LPV or MCV or between WUV and KIV. There was considerable sero-crossreactivity between SV40 and BKV, and to a lesser extent, between SV40 and JCV VP1 proteins. After correcting for crossreactivity, the SV40 seroprevalence was approximately 2%. The seroprevalence in children under 21 years of age (n = 721) for all Pys was similar to that of the adult population, suggesting that primary exposure to these viruses likely occurs in childhood.

Figure 1. Age-specific seroprevalence detected in a Denver, CO, USA study population (n = 2222) for 7 polyomaviruses known to infect humans.

A) SV40 (seroreactivity prior to competition with BKV and JCV VP1 proteins; Figure 3, Table S1); B) BKV; C) JCV; D) LPV; E) KIV; F) WUV; G) MCV isolate 350; H) MCV isolate 339. Standard error bars are shown.

Figure 2. Seroreactivity to VP1 proteins after competition with soluble heterologous VP1 pentamers.

A) SV40 seroreactivity competed with BKV; B) BKV seroreactivity competed with SV40; C) KIV seroreactivity competed with WUV; D) WUV seroreactivity competed with KIV; E) MCV isolate 350 seroreactivity competed with MCV isolate 339 and LPV; F) MCV isolate 339 seroreactivity competed with MCV isolate 350 and LPV; and G) LPV seroreactivity competed with MCV isolates 350 and 339. All capsid proteins were competed with themselves as well as with soluble GST as controls.

Figure 3. SV40 seroreactive samples competed with JCV and BKV VP1 proteins.

195 samples exhibiting initial SV40 seroreactivity (Figure 1A) were re-analyzed after pre-incubation with soluble BKV and/or JCV VP1. The percentages indicate the number of samples for which SV40 seroreactivity was eliminated by the designated pre-incubation conditions. No competition was observed for 43/195 (23%) of the samples.

Figure 4. Genetic variability of VP1 proteins among polyomaviruses.

A) phylogenetic analysis of 17 known polyomaviruses : B) Crystal structure of VP1 monomer derived from pdb id 3BWQ. PyMOL [46] was used to illustrate the surface variable loop regions C) amino acid primary sequence alignments of VP1 variable loop regions for SV40 and BKV, LPV and MCV, and KIV and WUV.