Our results show the occurrence of MCPyV DNA rather commonly in sera from the elderly. The source of viral DNA in their blood is unknown. As the previously identified polyomaviruses JCV and BKV do occur at increased frequencies in blood and lymphoid tissue during host immunosuppression, and the same has been reported in some studies for the newly discovered KIPyV and WUPyV [35–37], it is tempting to speculate that with increasing age MCPyV may reactivate more often, causing viremia, especially as hematolymphoid cells may harbour MCPyV . The potential in elderly individuals for MCPyV to replicate and be released into serum under special circumstances deserves further investigation.
A study of 840 serum samples for MCPyV revealed only one sample from a leukemic child to be PCR-positive; more often viral DNA was detected in tonsillar tissue of adults . In a study of 635 NPA samples with exactly the same primers and probes as ours, more adults (particularly the elderly) than children were MCPyV positive . Our high prevalence of MCPyV DNA among the elderly is in agreement with the findings of Goh et al. showing in NPAs MCPyV DNA more frequently among the elderly .
As in several other studies, viral DNA was detectable in low copy numbers, however, making the interpretation of positive results challenging [17, 32, 39, 40]. According to others’ positivity criteria concerning VP1 and LT PCRs [32, 39, 40], we concluded six samples as being unequivocally positive for MCPyV. However, all 25 amplicons from the LT or VP PCRs contained the correct sequence, and the 437 negative controls (62 for DNA extraction plus 375 for qPCR) were always negative, suggesting that also the single-PCR positives were true positives. Divergent sequences among the circulating viruses could perhaps cause false negativity in the PCRs, or the low viral amounts could lead to stochastic variance in detection.
Among the 72 MCPyV PCR-positive patients 15 were MCPyV VP1 IgG negative. One possible explanation for this difference, in light of the ubiquitous presence of MCPyV DNA in superficial skin, is contamination of the needle piercing the skin during sampling. This deserves to be explored.
Of note, MCPyV detection rates by LT1, LT3, and VP1-region primers have invariably shown mutual discordance among samples of various entities [1, 32, 39, 40]. We used primers from both the VP1 and LT regions of MCPyV and reasoned that the presence of both genes, capsid VP1 and oncogenic LT, would better indicate the presence of infectious virions, hence the stringent criterion of coupled LT and VP1 positivity for MCPyV detection by these assays. Interestingly, we found a positive association between MCPyV VP1-PCR but not LT1-PCR positivity and chronic respiratory disease. However, any conclusions about MCPyV pathogenicity in the respiratory tract cannot be drawn without epidemiologic support and further investigation with different sample types. Furthermore, it is difficult to resolve whether the higher prevalence by the VP1 assay was due to increased sensitivity or to a difference in genome identity sequences among the MCPyV strains.
The prevalence of MCPyV antibody positivity increases with age throughout life [18–21, 41, 42]. Our MCPyV serology results also showed that the majority of the elderly have been exposed to MCPyV with similar seroprevalences in all subgroups.
Taken together, MCPyV DNA appeared in serum in low copy numbers in many aging individuals. Serological results have shown that MCPyV infection is common, but only rarely leads to MCC. The presence of the virus alone is insufficient for tumor development. While MCC tumors require specific mutations (both T antigen truncation and genomic integration) , and in most cases immunosuppression, additional risk factors and viral changes are required before clinically apparent MCC emerges.
TSPyV is a ubiquitous virus that frequently infects the general population. To determine the exposure history and activity of infection among the aging, we conducted a survey by molecular and serologic tests. In contrast to MCPyV, no TSPyV DNA appeared in the elderly subjects’ sera. For one explanation of these negative PCR findings, TSPyV viremia may be of short duration. Whether TSPyV infections are able to persist is unknown, but likely, based on results for other polyomavirus infections. Our TSPyV IgG data confirmed two recent serologic reports showing TSPyV circulation in the general population [28, 29]. The seroprevalence we found for TSPyV among the elderly was high (>60%) with no variation according to advancing age, and comparable with that for MCPyV.