Cytomegalovirus in children undergoing haematopoietic stem cell transplantation: a diagnostic and therapeutic approach to antiviral resistance

Hume, John C.; Sweeney, Emma L.; Lowry, Kym; Fraser, Chris; Clark, Julia; Whiley, David M.; Irwin, Adam

doi:10.3389/fped.2023.1180392

Cited by 1 publication

(1 citation statement)

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“…Two had resistance mutations in both genes, while one isolate had resistance mutation only in the UL97 gene [ 95 ]. The complexity of virus populations circulating in congenitally infected patients might be due to the immature neonatal immune system and suggests a need for more frequent resistance testing, preferably by NGS technology [ 96 , 97 , 98 ].…”

Section: Prevalence Of Hcmv Drug Resistance Worldwidementioning

confidence: 99%

Human Cytomegalovirus (HCMV) Genetic Diversity, Drug Resistance Testing and Prevalence of the Resistance Mutations: A Literature Review

Grgic,

Gorenec

2024

TropicalMed

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Human cytomegalovirus (HCMV) is a pathogen with high prevalence in the general population that is responsible for high morbidity and mortality in immunocompromised individuals and newborns, while remaining mainly asymptomatic in healthy individuals. The HCMV genome is 236,000 nucleotides long and encodes approximately 200 genes in more than 170 open reading frames, with the highest rate of genetic polymorphisms occurring in the envelope glycoproteins. HCMV infection is treated with antiviral drugs such as ganciclovir, valganciclovir, cidofovir, foscarnet, letermovir and maribavir targeting viral enzymes, DNA polymerase, kinase and the terminase complex. One of the obstacles to successful therapy is the emergence of drug resistance, which can be tested phenotypically or by genotyping using Sanger sequencing, which is a widely available but less sensitive method, or next-generation sequencing performed in samples with a lower viral load to detect minority variants, those representing approximately 1% of the population. The prevalence of drug resistance depends on the population tested, as well as the drug, and ranges from no mutations detected to up to almost 50%. A high prevalence of resistance emphasizes the importance of testing the patient whenever resistance is suspected, which requires the development of more sensitive and rapid tests while also highlighting the need for alternative therapeutic targets, strategies and the development of an effective vaccine.

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