Functional properties of measles virus proteins derived from a subacute sclerosing panencephalitis patient who received repeated remdesivir treatments

Katharina S. Schmitz, Kim Handrejk, Lelde Liepina, Lisa Bauer, Griffin D. Haas, Fabienne van Puijfelik, Edwin J. B. Veldhuis Kroeze, Marta Riekstina, Jurgis Strautmanis, Huyen Cao, Robert M. Verdijk, Corine H. Geurtsvankessel, Sander van Boheemen, Debby van Riel, Benhur Lee, Matteo Porotto, Rik L. de Swart, Rory D. de Vries*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Downloads (Pure)

Abstract

Subacute sclerosing panencephalitis (SSPE) is a rare but fatal late neurological complication of measles, caused by persistent measles virus (MeV) infection of the central nervous system. There are no drugs approved for the treatment of SSPE. Here, we followed the clinical progression of a 5-year-old SSPE patient after treatment with the nucleoside analog remdesivir, conducted a post-mortem evaluation of the patient’s brain, and characterized the MeV detected in the brain. The quality of life of the patient transiently improved after the first two courses of remdesivir, but a third course had no further clinical effect, and the patient eventually succumbed to his condition. Post-mortem evaluation of the brain displayed histopathological changes including loss of neurons and demyelination paired with abundant presence of MeV RNA-positive cells throughout the brain. Next-generation sequencing of RNA isolated from the brain revealed a complete MeV genome with mutations that are typically detected in SSPE, characterized by a hypermutated M gene. Additional mutations were detected in the polymerase (L) gene, which were not associated with resistance to remdesivir. Functional characterization showed that mutations in the F gene led to a hyperfusogenic phenotype predominantly mediated by N465I. Additionally, recombinant wild-type-based MeV with the SSPE-F gene or the F gene with the N465I mutation was no longer lymphotropic but instead efficiently disseminated in neural cultures. Altogether, this case encourages further investigation of remdesivir as a potential treatment of SSPE and highlights the necessity to functionally understand SSPE-causing MeV.

Original languageEnglish
Pages (from-to)e0187423
Number of pages19
JournalJournal of Virology
Volume98
Issue number3
Early online date8 Feb 2024
DOIs
Publication statusPublished - Mar 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 Schmitz et al.

Fingerprint

Dive into the research topics of 'Functional properties of measles virus proteins derived from a subacute sclerosing panencephalitis patient who received repeated remdesivir treatments'. Together they form a unique fingerprint.

Cite this