Compartmentalization of a Multidrug-Resistant Cytomegalovirus UL54 Mutant in a Stem Cell Transplant Recipient with Encephalitis.
Acyclovir
/ pharmacology
Antibiotic Prophylaxis
/ methods
Antiviral Agents
/ pharmacology
Cerebrospinal Fluid
/ virology
Cytomegalovirus
/ genetics
Cytomegalovirus Infections
/ cerebrospinal fluid
Drug Resistance, Multiple, Viral
/ genetics
Encephalitis, Viral
/ cerebrospinal fluid
Female
Graft Rejection
/ immunology
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Immediate-Early Proteins
/ genetics
Immunosuppression Therapy
/ adverse effects
Middle Aged
Mutation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ immunology
Viral Proteins
/ genetics
Cytomegalovirus
cerebrospinal fluid
compartmentalization
drug resistance
encephalitis
hematopoietic stem cell transplantation
recombinant phenotyping
replicative capacity
three-dimensional modeling
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
13 09 2019
13 09 2019
Historique:
received:
27
03
2019
accepted:
10
06
2019
pubmed:
15
6
2019
medline:
28
5
2020
entrez:
15
6
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31199457
pii: 5519111
doi: 10.1093/infdis/jiz298
pmc: PMC6743826
doi:
Substances chimiques
Antiviral Agents
0
Immediate-Early Proteins
0
UL54 protein, herpes simplex virus type II
0
Viral Proteins
0
Acyclovir
X4HES1O11F
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1302-1306Subventions
Organisme : CIHR
ID : 148361
Pays : Canada
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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