Abstract
Infections due to resistant human cytomegalovirus (CMV) are an emerging problem, particularly in immunocompromised hosts. When managing such patients, clinicians should be aware of the possibility of developing CMV antiviral resistance, especially while on prolonged therapy or if severe immunosuppression is present. CMV resistance to current antiviral agents is mediated by alterations in either the UL97 kinase or DNA polymerase, encoded by the UL97 and UL54 genes, respectively. UL97 mutations are capable of conferring resistance to ganciclovir, while UL54 mutations can impart resistance to ganciclovir, cidofovir, and foscarnet. If treatment failure is suspected to be due to antiviral resistance, CMV resistance analysis should be obtained. Phenotypic resistance assays performed on clinical isolates measure antiviral susceptibilities directly, but are laborious and time-consuming. Therefore, genotypic resistance analysis has become the more common means of diagnosing CMV resistance. Mutations in UL97 or UL54 may be clinically associated with resistance, but their effect on antiviral susceptibility must be confirmed by marker transfer techniques such as recombinant phenotyping.
Keywords: Cytomegalovirus, cidofovir, foscarnet, ganciclovir, recombinant phenotyping, resistance, valganciclovir, Phenotypic resistance assays, antiviral resistance, antiretroviral therapy, maintenance therapy, nephrotoxicity, immunodeficiency syndrome, bacterial artificial chromosome (BAC), phylogenetic relationships
Infectious Disorders - Drug Targets
Title: The Genetic Basis of Human Cytomegalovirus Resistance and Current Trends in Antiviral Resistance Analysis
Volume: 11 Issue: 5
Author(s): S. H. James and M. N. Prichard
Affiliation:
Keywords: Cytomegalovirus, cidofovir, foscarnet, ganciclovir, recombinant phenotyping, resistance, valganciclovir, Phenotypic resistance assays, antiviral resistance, antiretroviral therapy, maintenance therapy, nephrotoxicity, immunodeficiency syndrome, bacterial artificial chromosome (BAC), phylogenetic relationships
Abstract: Infections due to resistant human cytomegalovirus (CMV) are an emerging problem, particularly in immunocompromised hosts. When managing such patients, clinicians should be aware of the possibility of developing CMV antiviral resistance, especially while on prolonged therapy or if severe immunosuppression is present. CMV resistance to current antiviral agents is mediated by alterations in either the UL97 kinase or DNA polymerase, encoded by the UL97 and UL54 genes, respectively. UL97 mutations are capable of conferring resistance to ganciclovir, while UL54 mutations can impart resistance to ganciclovir, cidofovir, and foscarnet. If treatment failure is suspected to be due to antiviral resistance, CMV resistance analysis should be obtained. Phenotypic resistance assays performed on clinical isolates measure antiviral susceptibilities directly, but are laborious and time-consuming. Therefore, genotypic resistance analysis has become the more common means of diagnosing CMV resistance. Mutations in UL97 or UL54 may be clinically associated with resistance, but their effect on antiviral susceptibility must be confirmed by marker transfer techniques such as recombinant phenotyping.
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Cite this article as:
H. James S. and N. Prichard M., The Genetic Basis of Human Cytomegalovirus Resistance and Current Trends in Antiviral Resistance Analysis, Infectious Disorders - Drug Targets 2011; 11 (5) . https://dx.doi.org/10.2174/187152611797636668
DOI https://dx.doi.org/10.2174/187152611797636668 |
Print ISSN 1871-5265 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3989 |
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