Drug-resistant cytomegalovirus: clinical implications of specific mutations

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: Cytomegalovirus (CMV) infection can be refractory to antiviral treatment. Although refractoriness can be due impaired host immunity, it can also be due to viral mutations that confer antiviral drug resistance. This article provides a succinct review of mutations in CMV genes that confer drug resistance, and offer guidance on clinical management. RECENT FINDINGS: Recent advances in medical and research technology have confirmed traditional mutations and identified novel ones that confer resistance to current antiviral drugs. Resistance to ganciclovir is commonly predicted by mutations in UL97, which encode for viral kinase that catalyzes its phosphorylation. Mutations in UL54, which encode for CMV DNA polymerase, confer resistance (or cross-resistance) to ganciclovir, cidofovir and/or foscarnet. Resistance to letermovir, the new drug approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients, has emerged and mapped most commonly to mutations in UL56 and less commonly UL51 and UL89, the gene complex that encode for viral terminase. SUMMARY: Mutations in CMV genes can be selected during antiviral drug exposure, and manifests phenotypically as nonresponsive drug-resistant disease. Knowledge of specific mutations informs clinicians in selecting appropriate antivirals for managing transplant patients with CMV disease.

Original languageEnglish (US)
Pages (from-to)388-394
Number of pages7
JournalCurrent opinion in organ transplantation
Volume23
Issue number4
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

Fingerprint

Cytomegalovirus
Mutation
Pharmaceutical Preparations
Antiviral Agents
Ganciclovir
Viral Drug Resistance
Foscarnet
Genes
Transplants
Cytomegalovirus Infections
DNA-Directed DNA Polymerase
Hematopoietic Stem Cells
Drug Resistance
Biomedical Research
Immunity
Phosphotransferases
Phosphorylation
Technology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation

Cite this

Drug-resistant cytomegalovirus : clinical implications of specific mutations. / Razonable, Raymund R.

In: Current opinion in organ transplantation, Vol. 23, No. 4, 01.08.2018, p. 388-394.

Research output: Contribution to journalArticle

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abstract = "PURPOSE OF REVIEW: Cytomegalovirus (CMV) infection can be refractory to antiviral treatment. Although refractoriness can be due impaired host immunity, it can also be due to viral mutations that confer antiviral drug resistance. This article provides a succinct review of mutations in CMV genes that confer drug resistance, and offer guidance on clinical management. RECENT FINDINGS: Recent advances in medical and research technology have confirmed traditional mutations and identified novel ones that confer resistance to current antiviral drugs. Resistance to ganciclovir is commonly predicted by mutations in UL97, which encode for viral kinase that catalyzes its phosphorylation. Mutations in UL54, which encode for CMV DNA polymerase, confer resistance (or cross-resistance) to ganciclovir, cidofovir and/or foscarnet. Resistance to letermovir, the new drug approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients, has emerged and mapped most commonly to mutations in UL56 and less commonly UL51 and UL89, the gene complex that encode for viral terminase. SUMMARY: Mutations in CMV genes can be selected during antiviral drug exposure, and manifests phenotypically as nonresponsive drug-resistant disease. Knowledge of specific mutations informs clinicians in selecting appropriate antivirals for managing transplant patients with CMV disease.",
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