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

J Infect Dis. 2019 Sep 13;220(8):1302-1306. doi: 10.1093/infdis/jiz298.

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: Cytomegalovirus; cerebrospinal fluid; compartmentalization; drug resistance; encephalitis; hematopoietic stem cell transplantation; recombinant phenotyping; replicative capacity; three-dimensional modeling.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / pharmacology
  • Acyclovir / therapeutic use
  • Antibiotic Prophylaxis / methods
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Cerebrospinal Fluid / virology
  • Cytomegalovirus / genetics*
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / cerebrospinal fluid
  • Cytomegalovirus Infections / diagnosis*
  • Cytomegalovirus Infections / prevention & control
  • Cytomegalovirus Infections / virology
  • Drug Resistance, Multiple, Viral / genetics*
  • Encephalitis, Viral / cerebrospinal fluid
  • Encephalitis, Viral / diagnosis*
  • Encephalitis, Viral / prevention & control
  • Encephalitis, Viral / virology
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immediate-Early Proteins / genetics
  • Immunosuppression Therapy / adverse effects
  • Middle Aged
  • Mutation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Viral Proteins / genetics

Substances

  • Antiviral Agents
  • Immediate-Early Proteins
  • UL54 protein, herpes simplex virus type II
  • Viral Proteins
  • Acyclovir

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