title: In vitro susceptibility of adenovirus to antiviral drugs is species-dependent.
abstract: Adenovirus infections are a frequent and serious complication following allogeneic haematopoietic stem cell transplantation (HSCT). The antiviral drugs cidofovir and ribavirin have been used as first-line therapy for disseminated infections with variable results. In the present study, in vitro susceptibility to these two drugs was evaluated on HEp-2 cells in adenovirus reference strains representing serotypes of each of the six species and in clinical isolates. Susceptibility to cidofovir was comparable between species with inhibition of replication of all tested serotypes in a narrow dose range (IC50=17-81 microM). However, susceptibility to ribavirin was highly dependent on the species. Serotypes from species A, B, D, E and F were all resistant to ribavirin (IC50=396 to >500 microM). Only replication of serotypes from species C was inhibited by ribavirin (IC50=48-108 microM). This species-dependent susceptibility of adenovirus to ribavirin was confirmed in clinical isolates. When tested on other cell lines (PLC, A549 and 293), all species were revealed to be resistant to ribavirin. If our in vitro findings are predictive of virological responses in vivo, these results suggest that ribavirin would not be effective for management of non-C species adenovirus infections after HSCT.
authors.affiliation: Laboratory of Virology, Edouard Herriot Hospital, Lyon, France. fmorfin@sante.univ-lyon1.fr
authors.forename: Florence
authors.initials: F
authors.lastname: Morfin
authors.forename: Sophie
authors.initials: S
authors.lastname: Dupuis-Girod
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Mundweiler
authors.forename: Delphine
authors.initials: D
authors.lastname: Falcon
authors.forename: David
authors.initials: D
authors.lastname: Carrington
authors.forename: Petr
authors.initials: P
authors.lastname: Sedlacek
authors.forename: Marc
authors.initials: M
authors.lastname: Bierings
authors.forename: Petr
authors.initials: P
authors.lastname: Cetkovsky
authors.forename: Aloys C M
authors.initials: AC
authors.lastname: Kroes
authors.forename: Maaoorten J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: Danielle
authors.initials: D
authors.lastname: Thouvenot
mesh_terms: D000258:Adenovirus Infections, Human / Q000821:virology; D000260:Adenoviruses, Human / Q000187:drug effects*; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D024882:Drug Resistance, Viral; D006801:Humans; D008826:Microbial Sensitivity Tests; D063065:Organophosphonates / Q000494:pharmacology* / Q000633:toxicity; D012254:Ribavirin / Q000494:pharmacology* / Q000633:toxicity; D013045:Species Specificity
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D012254:Ribavirin; D003596:Cytosine; D000077404:Cidofovir