title: Antiviral effect of cidofovir on parvovirus B19 replication.
abstract: Parvovirus B19 (B19V) is a human ssDNA virus responsible for a wide range of clinical manifestations, still lacking for a specific antiviral therapy. The identification of compounds active against B19V may add therapeutic options to the treatment of B19V infections, that now entirely relies on symptomatic treatments. In the search for compounds possibly inhibiting B19V replication, a particular focus was raised to cidofovir, an acyclic nucleoside phosphonate broadly active against dsDNA viruses. The present study was aimed at evaluating the effect of cidofovir against B19V in two model systems, the UT7/EpoS1 cell line and erythroid progenitor cells (EPC), generated from peripheral blood mononuclear cells. Experiments were carried out at different multiplicity of infections and cidofovir concentrations (0-500 μM) during a course of infection. The effects of cidofovir on B19V replication were assessed by qPCR assays while influence of cidofovir on host cells was measured by cell proliferation and viability assays. Our findings demonstrated that cidofovir has a relevant inhibiting activity on B19V replication within infected UT7/EpoS1, and that the effect on B19V DNA amounts is dose-dependent allowing for the determination of EC50 and EC90 values (7.45-41.27 μM, and 84.73-360.7 μM, respectively). In EPCs, that constitute a cellular population close to the natural target cells in bone marrow, the inhibitory effect was demonstrated to a lesser extent, however provoking a significant reduction on B19V DNA amounts at 500 μM (68.2-92.8%). To test infectivity of virus released from EPCs cultured in the presence of cidofovir, cell culture supernatants were used as inoculum for a further course of infection in UT7/EpoS1 cells, indicating a significant reduction in viral infectivity at 500 μM cidofovir. Since the drug did not interfere with the overall cellular DNA synthesis and metabolic activity, the observed effect of cidofovir could be likely related to a specific inhibition of B19V replication.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonvicini
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Bua
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Manaresi
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy; S.Orsola-Malpighi Hospital - Microbiology, University of Bologna, Bologna, Italy. Electronic address: giorgio.gallinella@unibo.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gallinella
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D015139:Blotting, Southern; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000821:virology; D063065:Organophosphonates / Q000494:pharmacology*; D016732:Parvovirus B19, Human / Q000187:drug effects* / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir
keywords: Cidofovir; Parvovirus B19; Quantitative PCR; Replication inhibition