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Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients

In pediatric and adult patients after stem cell transplantation (SCT) disseminated infections caused by human cytomegalovirus (HCMV) can cause life threatening diseases. For treatment, the three antivirals ganciclovir (GCV), foscarnet (PFA) and cidofovir (CDV) are approved and most frequently used....

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Autores principales: Göhring, Katharina, Hamprecht, Klaus, Jahn, Gerhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348572/
https://www.ncbi.nlm.nih.gov/pubmed/25750703
http://dx.doi.org/10.1016/j.csbj.2015.01.003
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author Göhring, Katharina
Hamprecht, Klaus
Jahn, Gerhard
author_facet Göhring, Katharina
Hamprecht, Klaus
Jahn, Gerhard
author_sort Göhring, Katharina
collection PubMed
description In pediatric and adult patients after stem cell transplantation (SCT) disseminated infections caused by human cytomegalovirus (HCMV) can cause life threatening diseases. For treatment, the three antivirals ganciclovir (GCV), foscarnet (PFA) and cidofovir (CDV) are approved and most frequently used. Resistance to all of these antiviral drugs may induce a severe problem in this patient cohort. Responsible for resistance phenomena are mutations in the HCMV phosphotransferase-gene (UL97) and the polymerase-gene (UL54). Most frequently mutations in the UL97-gene are associated with resistance to GCV. Resistance against all three drugs is associated to mutations in the UL54-gene. Monitoring of drug resistance by genotyping is mostly done by PCR-based Sanger sequencing. For phenotyping with cell culture the isolation of HCMV is a prerequisite. The development of multidrug resistance with mutation in both genes is rare, but it is often associated with a fatal outcome. The manifestation of multidrug resistance is mostly associated with combined UL97/UL54-mutations. Normally, mutations in the UL97 gene occur initially followed by UL54 mutation after therapy switch. The appearance of UL54-mutation alone without any detection of UL97-mutation is rare. Interestingly, in a number of patients the UL97 mutation could be detected in specific compartments exclusively and not in blood.
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spelling pubmed-43485722015-03-07 Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients Göhring, Katharina Hamprecht, Klaus Jahn, Gerhard Comput Struct Biotechnol J Mini Review In pediatric and adult patients after stem cell transplantation (SCT) disseminated infections caused by human cytomegalovirus (HCMV) can cause life threatening diseases. For treatment, the three antivirals ganciclovir (GCV), foscarnet (PFA) and cidofovir (CDV) are approved and most frequently used. Resistance to all of these antiviral drugs may induce a severe problem in this patient cohort. Responsible for resistance phenomena are mutations in the HCMV phosphotransferase-gene (UL97) and the polymerase-gene (UL54). Most frequently mutations in the UL97-gene are associated with resistance to GCV. Resistance against all three drugs is associated to mutations in the UL54-gene. Monitoring of drug resistance by genotyping is mostly done by PCR-based Sanger sequencing. For phenotyping with cell culture the isolation of HCMV is a prerequisite. The development of multidrug resistance with mutation in both genes is rare, but it is often associated with a fatal outcome. The manifestation of multidrug resistance is mostly associated with combined UL97/UL54-mutations. Normally, mutations in the UL97 gene occur initially followed by UL54 mutation after therapy switch. The appearance of UL54-mutation alone without any detection of UL97-mutation is rare. Interestingly, in a number of patients the UL97 mutation could be detected in specific compartments exclusively and not in blood. Research Network of Computational and Structural Biotechnology 2015-02-10 /pmc/articles/PMC4348572/ /pubmed/25750703 http://dx.doi.org/10.1016/j.csbj.2015.01.003 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Mini Review
Göhring, Katharina
Hamprecht, Klaus
Jahn, Gerhard
Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients
title Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients
title_full Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients
title_fullStr Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients
title_full_unstemmed Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients
title_short Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients
title_sort antiviral drug- and multidrug resistance in cytomegalovirus infected sct patients
topic Mini Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348572/
https://www.ncbi.nlm.nih.gov/pubmed/25750703
http://dx.doi.org/10.1016/j.csbj.2015.01.003
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