title: Enhanced inhibition of parvovirus B19 replication by cidofovir in extendedly exposed erythroid progenitor cells.
abstract: Human parvovirus B19 (B19V) commonly induces self-limiting infections but can also cause severe clinical manifestations in patients with underlying haematological 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 500μM (viral inhibition 82%) and in serially infected EPCs cultures with passage of the virus progeny, constantly under drug exposure (viral inhibition 99%). In addition, a potent inhibitory effect against B19V (viral inhibition 92%) was assessed in a short-term infection of EPCs treated with CDV 500μM 1day before viral infection. In the evaluated experimental conditions, the enhanced effect of CDV against B19V might 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.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. Electronic address: francesca.bonvicini4@unibo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonvicini
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Bua
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Manaresi
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy; S.Orsola-Malpighi Hospital-Microbiology, Via Massarenti 9, 40138 Bologna, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gallinella
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000821:virology; D006801:Humans; D063065:Organophosphonates / Q000494:pharmacology*; D016732:Parvovirus B19, Human / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D061251:Primary Cell Culture; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir
keywords: Cidofovir; Human erythroid progenitor cells; Human parvovirus B19; qPCR