Virologie
MENURésistance du cytomégalovirus humain aux antiviraux Volume 1, issue 2, Mars - Avril 1997
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- Key words: Cytomegalovirus - Resistance - Ganciclovir - Foscarnet - Phosphotranferase - DNA polymerase.
- Page(s) : 95-102
- Published in: 1997
Emergence of cytomegalovirus (CMV) resistance to antiviral drugs occurs with an increasing frequency in immunocompromised patients receiving iterative or prolonged anti-CMV therapy and is becoming a major clinical problem. Resistant mutants are clinically relevant as recovery of such strains is associated with the progression of the disease. Moreover, it has been shown that mutants to ganciclovir (GCV) can disseminate and cause severe multifocal CMV disease. Resistance to GCV is the most frequently encountered in clinical settings, and is mainly due to impaired intra-cellular phosphorylation of the drug because of mutations in the UL97 gene leading to amino acid substitutions in domains VI, VIII and IX of phosphotransferase UL97. Mutations in gene UL54 encoding the viral DNA polymerase occur more rarely and lead to cross-resistance to cidofovir without affecting the sensitivity to foscarnet. Concerning foscarnet, two changes in UL54 have been shown to confer resistance, but mutants are not cross-resistant to GCV and cidofovir. In addition these UL54 changes are responsible for the slow growth of the clinical isolates in tissue culture. In vitro drug-susceptibility testing is time consuming and fastidious. A rapid genetic screening for the most frequent mutations directly responsible for phenotypic resistance is diagnostically useful and provides early information for monitoring the treatment.