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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.
AuthorsFlorence Morfin, Sophie Dupuis-Girod, Stéphanie Mundweiler, Delphine Falcon, David Carrington, Petr Sedlacek, Marc Bierings, Petr Cetkovsky, Aloys C M Kroes, Maaoorten J D van Tol, Danielle Thouvenot
JournalAntiviral therapy (Antivir Ther) Vol. 10 Issue 2 Pg. 225-9 ( 2005) ISSN: 1359-6535 [Print] England
PMID15865216 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • Organophosphonates
  • Ribavirin
  • Cytosine
  • Cidofovir
Topics
  • Adenovirus Infections, Human (virology)
  • Adenoviruses, Human (drug effects)
  • Antiviral Agents (pharmacology, toxicity)
  • Cell Line, Tumor
  • Cidofovir
  • Cytosine (analogs & derivatives, pharmacology, toxicity)
  • Drug Resistance, Viral
  • Humans
  • Microbial Sensitivity Tests
  • Organophosphonates (pharmacology, toxicity)
  • Ribavirin (pharmacology, toxicity)
  • Species Specificity

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