2026-04-17T04:02:50Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/2041232024-11-29T10:35:00Zcom_2072_1057col_2072_478917col_2072_478921
2024-11-29T10:35:00Z
urn:hdl:2445/204123
Genotypic and phenotypic study of antiviral resistance mutations in refractory cytomegalovirus infection
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
the Spanish Network for Research in Infectious Diseases (REIPI)
Group for the Study of Infection in Transplantation (GESITRA)
Citomegalovirus
Resistència als medicaments
Cytomegaloviruses
Drug resistance
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.
2024-11-29T10:35:00Z
2024-11-29T10:35:00Z
2023-12-04T18:21:55Z
2023-12-04T18:21:55Z
2022-11-01
2023-12-04T18:21:55Z
info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
http://hdl.handle.net/2445/204123
Versió postprint del document publicat a: https://doi.org/10.1093/infdis/jiac349
Journal of Infectious Diseases, 2022, vol. 226, num.9, p. 1528-1536
https://doi.org/10.1093/infdis/jiac349
(c) Marta Santos Bravo et al., 2022
info:eu-repo/semantics/openAccess
Oxford University Press
Articles publicats en revistes (Medicina)