Title: Characterization of a cidofovir-resistant HHV-6 mutant obtained by in vitro selection
Authors: Bonnafous, Pascale ×
Boutolleau, David
Naesens, Lieve
Deback, Claire
Gautheret-Dejean, Agnès
Agut, Henri #
Issue Date: Mar-2008
Publisher: Elsevier/North-Holland
Series Title: Antiviral Research vol:77 issue:3 pages:237-240
Abstract: Cidofovir (CDV) was used for in vitro selection of a human herpesvirus 6 (HHV-6) mutant with decreased susceptibility to this drug. The resulting mutant was highly resistant to CDV as compared to its sensitive counterpart (inhibitory concentration 50% (IC50): 213 microM versus 1.8 microM). Its replication fitness was not impaired. Genotypic characterization of the resistant virus revealed a mutation in the U38 gene encoding the viral DNA polymerase. The resulting R798I amino acid change was located in the conserved domain VII close to the highly conserved motif KKRY interacting with the DNA primer-template duplex, and is likely responsible for the high-level resistance to CDV, even though a definite virological and/or biochemical confirmation is required. The possible emergence of such changes in HHV-6 DNA polymerase in patients receiving CDV therapy should be taken into account in the treatment of HHV-6 infections.
ISSN: 0166-3542
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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