We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Genotypic and Phenotypic Study of Antiviral Resistance Mutations in Refractory Cytomegalovirus Infection.
- Authors
Bravo, Marta Santos; Plault, Nicolas; Sánchez-Palomino, Sonsoles; Rodríguez, Cristina; Gabriel, Mireia Navarro; Mosquera, María Mar; Avilés, Francesc Fernández; Suarez-Lledó, María; Rovira, Montserrat; Bodro, Marta; Moreno, Asunción; Linares, Laura; Cofan, Frederic; Berengua, Carla; Esteva, Cristina; Cordero, Elisa; Martin-Davila, Pilar; Aranzamendi, Maitane; Jiménez, Ana Belén Pérez; Vidal, Elisa
- Abstract
<bold>Background: </bold>This study describes the genotypic and phenotypic characterization of novel human cytomegalovirus (HCMV) genetic variants of a cohort of 94 clinically resistant HCMV patients.<bold>Methods and Results: </bold>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.<bold>Conclusions: </bold>Extending mutation databases is crucial to optimize treatments and to improve the assessment of patients with resistant/refractory HCMV infection.
- Subjects
GANCICLOVIR; PROTEINS; CYTOMEGALOVIRUSES; GENETIC mutation; CYTOMEGALOVIRUS diseases; ANTIVIRAL agents; RESEARCH funding; DRUG resistance in microorganisms; DNA polymerases; PHENOTYPES
- Publication
Journal of Infectious Diseases, 2022, Vol 226, Issue 9, p1528
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiac349