Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.
Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.
Pérez
J L
JL
Servei de Microbiologia, Ciutat Sanitària i Universitària de Bellvitge, Spain. josel.perez@csub.scs.es
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077404:Cidofovir; D003062:Codon / Q000235:genetics; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology*; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D017245:Foscarnet / Q000494:pharmacology / Q000627:therapeutic use; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use; D005814:Genes, Viral; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology / Q000627:therapeutic use; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D015678:Viral Structural Proteins / Q000235:genetics
D000998:Antiviral Agents; D003062:Codon; D019384:Nucleic Acid Synthesis Inhibitors; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D014764:Viral Proteins; D015678:Viral Structural Proteins; D017245:Foscarnet; D003596:Cytosine; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D000077404:Cidofovir; D015774:Ganciclovir