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Scientific article
English

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

Published inThe Journal of Infectious Diseases, vol. 220, no. 8, p. 1302-1306
Publication date2019
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 use
  • Antibiotic Prophylaxis/methods
  • Antiviral Agents/pharmacology/therapeutic use
  • Cerebrospinal Fluid/virology
  • Cytomegalovirus/genetics/isolation & purification
  • Cytomegalovirus Infections/cerebrospinal fluid/diagnosis/prevention & control/virology
  • Drug Resistance, Multiple, Viral/genetics
  • Encephalitis, Viral/cerebrospinal fluid/diagnosis/prevention & control/virology
  • Female
  • Graft Rejection/immunology/prevention & control
  • Hematopoietic Stem Cell Transplantation/adverse effects
  • Humans
  • Immediate-Early Proteins/genetics
  • Immunosuppression/adverse effects
  • Middle Aged
  • Mutation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology/therapy
  • Viral Proteins/genetics
Citation (ISO format)
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
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Article (Published version)
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Identifiers
ISSN of the journal0022-1899
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