title: The biology of cytomegalovirus drug resistance.
abstract: OBJECTIVE
  This review assesses recently published data on cytomegalovirus (CMV) antiviral drug resistance.
  
  
  RESULTS
  Resistance is typically encountered after prolonged ganciclovir treatment for posttransplant primary CMV infection and is diagnosed by the detection of characteristic mutations in the viral UL97 kinase and UL54 DNA polymerase genes in clinical specimens. One of seven canonical UL97 mutations is detected in most cases of ganciclovir resistance, but many viral sequence variants of unknown relevance are being reported after drug exposure in vitro and in vivo. Rapid technical advances in recombinant phenotyping have shown that many of these variants confer no detectable drug resistance, whereas some unusual resistance mutations are newly confirmed. All currently marketed CMV antiviral drugs, including foscarnet and cidofovir, target the viral DNA polymerase, and cross-resistance may result from some UL54 mutations. To decrease cross-resistance and toxicity, there is an ongoing effort to develop anti-CMV drugs with different resistance pathways and alternative targets, such as the UL97 kinase or UL56-UL89 terminase enzymes.
  
  
  CONCLUSIONS
  An increasing volume of information correlating CMV genotypes and drug susceptibility phenotypes is becoming available. This will improve the interpretation of sequence-based assays currently used for clinical diagnosis and guide the development of new antiviral drugs.
authors: Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA.
authors: Morgan
authors: M
authors: Hakki
authors: Sunwen
authors: S
authors: Chou
mesh_terms: D003587:Cytomegalovirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics
chemical_list: C109367:UL54 protein, Human herpesvirus 5; D014764:Viral Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C075365:ganciclovir kinase; D004259:DNA-Directed DNA Polymerase