Mammalian polyomaviruses are characterized by establishing persistent infections in healthy hosts and generally causing clinical disease only in hosts whose immune systems are compromised. Despite the fact that these viruses were discovered decades ago, our knowledge of the mechanisms that govern viral persistence and reactivation is limited. Whereas mouse polyomavirus has been studied in a fair amount of detail, our understanding of the human viruses in particular is mostly inferred from experiments aimed at addressing other questions. In this review, we summarize the state of our current knowledge, draw conclusions when possible, and suggest areas that are in need of further study.

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