Progress in understanding cytomegalovirus drug resistance.
The molecular basis for cytomegalovirus drug resistance against currently used antivirals comprises two genetic loci. In the case of ganciclovir, mutations in both the UL97 protein kinase and UL64 DNA polymerase can lead to resistance, whereas for cidofovir and foscarnet only mutations in UL54 give rise to resistance. Clinically, resistance strains of cytomegalovirus appear after prolonged periods of antiviral therapy especially when treatment has been interrupted or is at sub-optimal doses. Knowledge of the replication dynamics of cytomegalovirus in vivo can be used to predict the virologic course of patients who develop resistance virus. Using such models, a good agreement between experimentally determined viral load and resistance patterns is observed.
Emery
V C
VC
Royal Free and University College Medical School, Rowland Hill Street, NW3 2PF, London, UK. vemery@rfc.ucl.ac.uk
D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics; D005544:Forecasting; D017245:Foscarnet / Q000494:pharmacology; D015774:Ganciclovir / Q000494:pharmacology; D006801:Humans; D015994:Incidence; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D017245:Foscarnet; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir