Characterization of the dynamics of human cytomegalovirus resistance to antiviral drugs by ultra-deep sequencing

Guermouche, Hélène; Burrel, Sonia; Mercier-Darty, Mélanie; Kofman, Thomas; Rogier, Olivier; Pawlotsky, Jean‐Michel; Boutolleau, David; Rodriguez, Christophe

doi:10.1016/j.antiviral.2019.104647

Cited by 15 publications

(13 citation statements)

References 31 publications

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“…This approach has the great advantage of allowing resistant populations and strain numbers to be assessed across the whole viral genome in a single assay. Studies employing analysis of individual HCMV genes by PCR and HTS to detect antiviral resistance mutations in HCMV infections have been reported (Sahoo et al, 2013;Chou et al, 2014;Guermouche et al, 2020), but none has applied a wholegenome approach. Moreover, sophisticated bioinformatic tools have recently been developed to facilitate accurate interrogation of HTS data for the presence of multiple HCMV strains (Suárez et al, 2019a,b).…”

Section: Introductionmentioning

confidence: 99%

Whole-Genome Approach to Assessing Human Cytomegalovirus Dynamics in Transplant Patients Undergoing Antiviral Therapy

Suárez

Blyth

et al. 2020

Front. Cell. Infect. Microbiol.

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Section: Introductionmentioning

confidence: 99%

Whole-Genome Approach to Assessing Human Cytomegalovirus Dynamics in Transplant Patients Undergoing Antiviral Therapy

Suárez

Blyth

et al. 2020

Front. Cell. Infect. Microbiol.

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“…The remaining cases were either found as minority variants or only in a few cases detected as the dominating mutant within 4 weeks of infection offset. This observation implies a clinical challenge in the timing and interpretation of NGS technology for the diagnosis of UL97-GCV-R and highlights the highly complex and dynamic interactions between the immunocompromised host and CMV [ 36 , 37 ]. To properly address this research question, larger, prospective, and better powered studies on UL97-GCV-R are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…The use of NGS enabled investigation of both dominant mutants and minor variants. However, the present study, as well as most other studies on CMV resistance mutations, is hampered by the low number of actual resistant cases to study [ 18 , 36 , 37 ]. Despite having a relatively large sample size, UL97-GCV-R is a rare event, emphasizing the need for larger multicenter studies.…”

Section: Discussionmentioning

confidence: 99%

Development and Dynamics of Cytomegalovirus UL97 Ganciclovir Resistance Mutations in Transplant Recipients Detected by Next-Generation Sequencing

Lodding

Jørgensen

Bennedbæk

et al. 2021

Open Forum Infectious Diseases

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Background (Val)ganciclovir resistance mutations in CMV UL97 (UL97-GCV-R) complicate anti-CMV therapy in recipients of solid organ and hematopoietic stem-cell transplants but comprehensive data on prevalence, emergence, and outcome are scarce. Methods Using next generation sequencing (NGS) (Illumina MiSeq platform), we analysed UL97-GCV-R in patients with available plasma samples and refractory CMV replication/DNAemia (n=87) containing viral loads ≥910 IU/mL. 21 patients with CMV DNAemia resolving under antiviral therapy were analysed as controls. Detected mutations were considered induced and of potential clinical significance if they increased by ≥10% compared to the first detected frequency, or if they had a maximum frequency ≥25%. Results 19/87 (21.8%) with refractory CMV replication had >1 UL97-GCV-R detected by NGS, in comparison to 0/21 of the controls (p=0.02). One third of the recipients had 2 or more induced UL97-GCV-R mutations. The most frequently induced mutations affected codons 595 (42% (8/19)), 594 (32% (6/19)) and 603 (32% (6/19)). C592G was present in all episodes of both cases and controls at frequencies <15%, but never induced. UL97-GCV-R tended to be more frequent in donor/recipient CMV IgG mismatch or following failure to complete primary prophylaxis, and many developed invasive CMV disease. Conclusion UL97-GCV-R is common among transplant patients with refractory CMV replication. Early testing by NGS allows for identification of major mutations at codons 595, 594 and 603, and exclude a major role of C592G in ganciclovir resistance. Large prospective studies on UL97-GCV-R are warranted.

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“…NGS tekniklerinin, Sanger tekniğine göre alt popülasyonları da saptayabilmesi, GCV direnci çalışmalarında daha duyarlı sonuçlar ortaya koymaktadır. Guermouche ve arkadaşlarının ultra derin sekanslama (UDS) tekniği kullanarak CMV antiviral direncini araştırdıkları bir çalışmada 18 , uzun süreli antiviral tedavi gören immün yetmezlikli hastalardan izole edilen CMV UL97 ve UL54 gen bölgelerinde minör ve majör varyant diziler saptanmış ve bu diziler, tedavi başarısızlığının bir nedeni olarak gösterilmiştir.…”

Section: Discussionunclassified

İmmün Yetmezlikli Hastalardan Elde Edilen Sitomegalovirüs İzolatlarındaki Gansiklovir Direncinin Araştırılması

et al. 2020

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Characterization of the dynamics of human cytomegalovirus resistance to antiviral drugs by ultra-deep sequencing

Cited by 15 publications

References 31 publications

Whole-Genome Approach to Assessing Human Cytomegalovirus Dynamics in Transplant Patients Undergoing Antiviral Therapy

Whole-Genome Approach to Assessing Human Cytomegalovirus Dynamics in Transplant Patients Undergoing Antiviral Therapy

Development and Dynamics of Cytomegalovirus UL97 Ganciclovir Resistance Mutations in Transplant Recipients Detected by Next-Generation Sequencing

İmmün Yetmezlikli Hastalardan Elde Edilen Sitomegalovirüs İzolatlarındaki Gansiklovir Direncinin Araştırılması

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