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Compartmentalization of a Multidrug-Resistant Cytomegalovirus UL54 Mutant in a Stem Cell Transplant Recipient with Encephalitis

Piret, Jocelyne
Pham, Van Dung
Hantz, Sébastien
Goyette, Nathalie
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Published in The Journal of infectious diseases. 2019, vol. 220, no. 8, p. 1302-1306
Abstract We report a case of cytomegalovirus encephalitis in a hematopoietic stem cell transplant recipient. A previously uncharacterized V787E mutation in UL54 was identified in cerebrospinal fluid but not plasma specimens. For the V787E recombinant virus, the half maximal effective concentrations for ganciclovir, foscarnet, and cidofovir were 8.6-, 3.4- and 2.9-fold higher than for wild-type virus, and the replicative capacity was lower. The introduction of a bulkier and negatively charged glutamate residue at position 787 could destabilize the finger domain of UL54 DNA polymerase. Viral genotyping of cerebrospinal fluid is warranted in subjects with cytomegalovirus encephalitis, owing to the low penetration of antivirals in this compartment.
Keywords Acyclovir/pharmacology/therapeutic useAntibiotic Prophylaxis/methodsAntiviral Agents/pharmacology/therapeutic useCerebrospinal Fluid/virologyCytomegalovirus/genetics/isolation & purificationCytomegalovirus Infections/cerebrospinal fluid/diagnosis/prevention & control/virologyDrug Resistance, Multiple, Viral/geneticsEncephalitis, Viral/cerebrospinal fluid/diagnosis/prevention & control/virologyFemaleGraft Rejection/immunology/prevention & controlHematopoietic Stem Cell Transplantation/adverse effectsHumansImmediate-Early Proteins/geneticsImmunosuppression/adverse effectsMiddle AgedMutationPrecursor Cell Lymphoblastic Leukemia-Lymphoma/immunology/therapyViral Proteins/genetics
PMID: 31199457
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Research groups Groupe Laurent Kaiser (virologie clinique) (668)
Leucémie et transplantation allogénique de cellules souches hématopoïétiques (982)
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PIRET, Jocelyne et al. Compartmentalization of a Multidrug-Resistant Cytomegalovirus UL54 Mutant in a Stem Cell Transplant Recipient with Encephalitis. In: The Journal of Infectious Diseases, 2019, vol. 220, n° 8, p. 1302-1306. doi: 10.1093/infdis/jiz298 https://archive-ouverte.unige.ch/unige:144861

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Deposited on : 2020-11-18

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