The biology of cytomegalovirus drug resistance

Research output: Contribution to journalReview articlepeer-review

68 Scopus citations

Abstract

PURPOSE OF REVIEW: This review assesses recently published data on cytomegalovirus (CMV) antiviral drug resistance. RECENT FINDINGS: 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. SUMMARY: 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.

Original languageEnglish (US)
Pages (from-to)605-611
Number of pages7
JournalCurrent Opinion in Infectious Diseases
Volume24
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • Antiviral therapy
  • Cytomegalovirus
  • Drug resistance

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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