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2022-11-01

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/204118

Genotypic and phenotypic study of antiviral resistance mutations in refractory cytomegalovirus infection

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https://doi.org/10.1093/infdis/jiac349

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Background This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients. Methods and results Antiviral-resistant mutations were detected in the UL97, UL54, and UL56 target genes of 25 of 94 (26.6%) patients. The genotype-phenotype correlation study resolved the status of 5 uncharacterized UL54 deoxyribonucleic acid polymerase (G441S, A543V, F460S, R512C, A928T) and 2 UL56 terminase (F345L, P800L) mutations found in clinical isolates. A928T conferred high, triple resistance to ganciclovir, foscarnet, and cidofovir, and A543V had 10-fold reduced susceptibility to cidofovir. Viral growth assays showed G441S, A543V, F345L, and P800L impaired viral growth capacities compared with wild-type AD169 HCMV. Three-dimensional modeling predicted A543V and A928T phenotypes but not R512C, reinforcing the need for individual characterization of mutations by recombinant phenotyping. Conclusions Extending mutation databases is crucial to optimize treatments and to improve the assessment of patients with resistant/refractory HCMV infection.

Matèries

Citomegalovirus, Resistència als medicaments

Matèries (anglès)

Cytomegaloviruses, Drug resistance

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Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (ISGlobal)
Articles publicats en revistes (Medicina)

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SANTOS BRAVO, Marta, Nicolas Plault, SÁNCHEZ-PALOMINO, Sonsoles, RODRÍGUEZ, Cristina, NAVARRO GABRIEL, Mireia, MOSQUERA, María mar, FERNÁNDEZ AVILÉS, Francesc, SUAREZ LLEDÓ, María, ROVIRA, Montserrat, BODRO, Marta, MORENO CAMACHO, Ma. asunción, LINARES, Laura, COFÁN PUJOL, Federico, BERENGUA, Carla, ESTEVA, Cristina, CORDERO, Elisa, MARTÍN DÁVILA, Pilar, ARANZAMENDI, Maitane, PÉREZ JIMÉNEZ, Ana belén, VIDAL, Elisa, FERNÁNDEZ SABÉ, Núria, LEN, Óscar, HANTZ, Sebastien, ALAIN, Sophie, MARCOS, Ma. angeles, Spanish Network for Research in Infectious Diseases (REIPI), Group for the Study of Infection in Transplantation (GESITRA). Genotypic and phenotypic study of antiviral resistance mutations in refractory cytomegalovirus infection. _Journal of Infectious Diseases_. 2022. Vol. 226, núm. 9, pàgs. 1528-1536. [consulta: 22 de gener de 2026]. ISSN: 0022-1899. [Disponible a: https://hdl.handle.net/2445/204118]

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