Inhibition of Parvovirus B19 replication by Cidofovir in extendedly exposed erythroid progenitor cells

Human parvovirus B19 (B19V) commonly induces self-limiting infections but can also cause severe clinical manifestations in patients with underlying hematological disorders or with immune system deficits. Currently, therapeutic options for B19V entirely rely on symptomatic and supportive treatments since a specific antiviral therapy is not yet available. Recently a first step in the research for active compounds inhibiting B19V replication has allowed identifying the acyclic nucleoside phosphonate cidofovir (CDV). Herein, the effect of CDV against B19V replication was characterized in human erythroid progenitor cells (EPCs) cultured and infected following different experimental approaches to replicate in vitro the infection of an expanding erythroid cell population in the bone marrow. B19V replication was selectively inhibited both in infected EPCs extendedly exposed to CDV 500 μM (viral inhibition 82%) and in serially infected EPCs cultures with passages of the viral progeny, constantly under drug pressure (viral inhibition >99%). In addition, a potent inhibitory effect against B19V (>92%) was assessed in a short-term infection of EPCs treated with CDV 500 μM prior to viral infection. This enhanced anti-B19V activity of CDV could be ascribed both to the increased intracellular drug concentration achieved by extended exposure, and to a progressive reduction in efficiency of the replicative process within treated EPCs population.