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

• Published in: The Journal of infectious diseases Vol. 220; no. 8; pp. 1302 - 1306
• Main Authors: Piret, Jocelyne, Schibler, Manuel, Pham, Van Dung, Hantz, Sébastien, Giannotti, Federica, Masouridi-Levrat, Stavroula, Kaiser, Laurent, Goyette, Nathalie, Alain, Sophie, Shi, Rong, Boivin, Guy
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 13.09.2019
• Subjects: Acyclovir - pharmacology; Acyclovir - therapeutic use; Antibiotic Prophylaxis - methods; Antiviral agents; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Antiviral drugs; Case reports; Cerebrospinal fluid; Cerebrospinal Fluid - virology; Cidofovir; Cytomegalovirus; Cytomegalovirus - genetics; Cytomegalovirus - isolation & purification; Cytomegalovirus Infections - cerebrospinal fluid; Cytomegalovirus Infections - diagnosis; Cytomegalovirus Infections - prevention & control; Cytomegalovirus Infections - virology; DNA-directed DNA polymerase; Drug resistance; Drug Resistance, Multiple, Viral - genetics; Encephalitis; Encephalitis, Viral - cerebrospinal fluid; Encephalitis, Viral - diagnosis; Encephalitis, Viral - prevention & control; Encephalitis, Viral - virology; Female; Foscarnet; Ganciclovir; Genotyping; Graft Rejection - immunology; Graft Rejection - prevention & control; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Humans; Immediate-Early Proteins - genetics; Immunosuppression - adverse effects; Life Sciences; Major and Brief Reports; Microbiology and Parasitology; Middle Aged; Multidrug resistance; Multidrug resistant organisms; Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Stem cell transplantation; Stem cells; Viral Proteins - genetics; Virology; VIRUSES; Cytomegalovirus; three-dimensional modeling; encephalitis; compartmentalization; recombinant phenotyping; cerebrospinal fluid; hematopoietic stem cell transplantation; drug resistance; replicative capacity
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiz298

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.