In Vitro and In Vivo Models for the Study of Human Polyomavirus Infection

Abstract

Developments of genome amplification techniques have rapidly expanded the family of human polyomaviruses (PyV). Following infection early in life, PyV persist in their hosts and are generally of no clinical consequence. High-level replication of PyV can occur in patients under immunosuppressive or immunomodulatory therapy and causes severe clinical entities, such as progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy or Merkel cell carcinoma. The characterization of known and newly-discovered human PyV, their relationship to human health, and the mechanisms underlying pathogenesis remain to be elucidated. Here, we summarize the most widely-used in vitro and in vivo models to study the PyV-host interaction, pathogenesis and anti-viral drug screening. We discuss the strengths and limitations of the different models and the lessons learned.

Keywords: animal models; entry; in vitro models; pathogenesis; polyomavirus; tropism.

Figure 1

Human PyV particles are composed of 72 pentamers of the capsid protein VP1, with one of the minor capsid proteins VP2 or VP3 in the center of each pentamer. The human PyV genome is divided into three regions: a non-coding region, containing the early and late promoters, transcription sites and the origin of replication; an early region encoding small T antigens (sT), large T antigens (LT) and alternatively-spliced LT antigens (LT’); and a late region encoding the viral structural proteins VP1, VP2 and VP3. Among human polyomaviruses, only BKPyV and JCPyV encode an agnoprotein (agno) upstream of VP1. Merkel cell PyV (MCPyV) does not encode the minor capsid protein VP3.