Drug Resistance and the UL97 Gene of Human Cytomegalovirus

1997 ◽  
pp. 180-192
Author(s):  
A. Zimmermann ◽  
D. Michel ◽  
T. Mertens
Keyword(s):  
Drug Resistance ◽  
Human Cytomegalovirus ◽  
Ul97 Gene

scholarly journals Sequencing of Cytomegalovirus UL97 Gene for Genotypic Antiviral Resistance Testing

2001 ◽  
Vol 45 (10) ◽  
pp. 2775-2780 ◽  
Author(s):  
Nell S. Lurain ◽  
Adriana Weinberg ◽  
Clyde S. Crumpacker ◽  
Sunwen Chou
Keyword(s):  
Drug Resistance ◽  
Clinical Isolates ◽  
Resistance Testing ◽  
Virus Infectivity ◽  
Resistance Mutations ◽  
Sequence Identity ◽  
Complete Sequences ◽  
Immunosuppressed Patients ◽  
Ul97 Gene ◽  
Genotypic Assay

ABSTRACT The widespread use of ganciclovir (GCV) to treat cytomegalovirus (CMV) infections in immunosuppressed patients has led to the development of drug resistance. Phenotypic assays for CMV drug resistance are presently too time-consuming to be therapeutically useful. To support the development of genotypic assays for GCV resistance, the complete sequences of the UL97 phosphotransferase genes in 28 phenotypically GCV-sensitive CMV clinical isolates were determined. The gene was found to be highly conserved, with nucleotide sequence identity among strains ranging from 98.6 to 100% and amino acid sequence identity of >99%. Primers for a genotypic assay were designed to amplify codons 400 to 707, because all known UL97 mutations conferring drug resistance occur at three sites within this region. This part of the UL97 gene was amplified from over 50 clinical isolates, and two sequencing reactions for the coding strand were successfully used to identify GCV resistance mutations. This genotypic assay can be performed in 48 h using genomic DNA extracted from cell monolayers at very low levels of virus infectivity, thus rapidly providing therapeutically useful results.

A Mass Spectrometry-based Method to Detect Antiviral Drug Resistance in Human Cytomegalovirus

2009 ◽  
Vol 82 (2) ◽  
pp. A51
Author(s):  
Clara Posthuma ◽  
Martha Van der Beek ◽  
Caroline Van der Blij ◽  
Willy Spaan ◽  
Louis Kroes ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Drug Resistance ◽  
Human Cytomegalovirus ◽  
Antiviral Drug ◽  
Antiviral Drug Resistance

scholarly journals Interstrain Variation in the Human Cytomegalovirus DNA Polymerase Sequence and Its Effect on Genotypic Diagnosis of Antiviral Drug Resistance

1999 ◽  
Vol 43 (6) ◽  
pp. 1500-1502 ◽  
Author(s):  
Sunwen Chou ◽  
Nell S. Lurain ◽  
Adriana Weinberg ◽  
Guang-Yung Cai ◽  
Prem L. Sharma ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Amino Acid ◽  
Dna Polymerase ◽  
Human Cytomegalovirus ◽  
Antiviral Drug ◽  
Resistance Mutations ◽  
Sequence Alignments ◽  
Coding Sequence ◽  
Antiviral Drug Resistance ◽  
Almost All

ABSTRACT The polymerase (pol) coding sequence was determined for 40 independent clinical cytomegalovirus isolates sensitive to ganciclovir and foscarnet. Sequence alignments showed >98% interstrain homology and amino acid variation in only 4% of the 1,237 codons. Almost all variation occurred outside of conserved functional domains where resistance mutations have been identified.

Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3286-3289
Author(s):  
Tobias Eckle ◽  
Lothar Prix ◽  
Gerhard Jahn ◽  
Thomas Klingebiel ◽  
Rupert Handgretinger ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Human Cytomegalovirus ◽  
Allogeneic Stem Cell Transplantation ◽  
Hcmv Infection ◽  
Antiviral Drug ◽  
Increased Risk

Three seropositive pediatric recipients of allogeneic stem cell transplantation out of a group of 42 patients receiving T-cell–depleted, unrelated transplants and 37 patients receiving T-cell–depleted, haploidentical transplants were monitored longitudinally for human cytomegalovirus (HCMV) infection and the emergence of antiviral drug resistance. Early in the posttransplant course, all 3 patients developed HCMV mutations conferring drug resistance to ganciclovir. One child additionally developed multidrug resistance to foscarnet and cidofovir, with mutations in the viral phosphotransferase gene (UL97) and the DNA-polymerase gene (UL54) being found. These data show that resistant HCMV infection does not necessarily correlate with a severe clinical outcome. The early detection of genotypic resistance up to 129 days before the emergence of phenotypic resistance and the dissociation of resistance patterns among different body sites emphasize the importance of genotypic analyses of different DNA specimens for an efficient antiviral therapy. T-cell–depleted children having transplantation might be at an increased risk for the development of drug resistance.

scholarly journals cmvdrg - An R package for Human Cytomegalovirus antiviral Drug Resistance Genotyping

2020 ◽  
Author(s):  
Oscar J Charles ◽  
Cristina Venturini ◽  
Judith Breuer
Keyword(s):  
Drug Resistance ◽  
Open Source ◽  
Human Cytomegalovirus ◽  
Antiviral Drug ◽  
R Package ◽  
Effective Vaccine ◽  
Analysis Tool ◽  
Resistance Mutations ◽  
Drug Resistance Genotyping ◽  
User Friendly

AbstractThe prevention and treatment of HCMV infection is based on the utilization of antiviral therapies as HCMV lacks an effective vaccine. The rise of drug resistance is therefore an increasing patient threat. We identified the need for an open source and comprehensive HCMV resistance mutations database, to support the research community in this area. Here we present “Cytomegalovirus Drug Resistance Genotyping” (cmvdrg), a freely available database contained within an easily accessible R package, which provides a succinct extraction of literature material in the form of a text file database. Additionally, cmvdrg includes methods for calling resistance in common sequencing files and an optional user-friendly web interface.AvailabilityThe cmvdrg package is freely available under the GNU GPL v3 license at https://github.com/ucl-pathgenomics/cmvdrg,One Sentence SummaryCurrently data regarding Human Cytomegalovirus resistant mutations are contained in unconnected literature sources, here we present an exhaustive open source database and analysis tool for the community.

Sign in / Sign up

Export Citation Format

Share Document