Aciclovir selects for ganciclovir-cross-resistance of human cytomegalovirus in vitro that is only in part explained by known mutations in the UL97 protein
D. Michel et al., Aciclovir selects for ganciclovir-cross-resistance of human cytomegalovirus in vitro that is only in part explained by known mutations in the UL97 protein, J MED VIROL, 65(1), 2001, pp. 70-76
Phenotypically, ganciclovir-resistant human cytomegalovirus strains could b
e selected by aciclovir as effectively as by ganciclovir in vitro. Three cl
inical human cytomegalovirus isolates with different sensitivities against
ganciclovir, aciclovir, foscarnet, and cidofovir, but without any mutation
in the viral UL97 protein known to confer ganciclovir resistance, were prop
agated each in duplicate in the presence of ganciclovir or aciclovir. After
drug selection, all 12 strains were less susceptible to ganciclovir (incre
ase of 50% focus reduction dose between 2.1- and 31.5-fold) but were still
sensitive to foscarnet and cidofovir; 7/12 exhibited a ganciclovir-resistan
t phenotype with a 50% focus reduction dose > 30 muM, and in 6 out of these
typical mutations in the UL97 coding region could be found by genotyping.
All four strains selected from one isolate carried the identical UL97 mutat
ion at amino acid position 460 (methionine to valine). The decreased sensit
ivity to ganciclovir and aciclovir in the other strains could neither be at
tributed to known UL97 mutations nor to mutations in the viral polymerase (
UL54), which have been reported to induce resistance. (C) 2001 Wiley-Liss,
Inc.