Measles-like hypermutation of a Newcastle disease virus drives fatal encephalitis during BCMA × CD3 T-cell-redirecting immunotherapy
Year: 2026
Type: article
Abstract: Newcastle disease virus (NDV or AOaV-1) is an avian paramyxovirus that typically causes only mild, self-limiting disease in humans. Here, we report fatal neuroinvasive AOaV-1 infection in a patient with multiple myeloma receiving maintenance therapy with teclistamab, daratumumab, and lenalidomide following frontline teclistamab-based treatment and autologous stem cell transplantation. Following rapidly progressive brainstem–cerebellar encephalitis and negative conventional microbiological testing, unbiased metagenomic RNA sequencing of a cerebellar biopsy identified AOaV-1 at high intraparenchymal abundance. Viral genome analysis revealed striking A-to-G and U-to-C substitutions selectively concentrated in the matrix gene, consistent with ADAR-mediated RNA editing. Long-read sequencing resolved two genetically distinct, independently hypermutated CNS haplotypes. Post-mortem analysis demonstrated widespread dissemination and continued viral diversification in multiple brain regions, whereas a peripheral urine sample contained a minimally mutated putative ancestral lineage. These findings support peripheral infection followed by CNS seeding and compartmentalized within-host evolution. The selective matrix-gene hypermutation closely parallels persistent measles virus infection in subacute sclerosing panencephalitis, revealing a shared mechanism of paramyxovirus adaptation to the CNS. Profound immunotherapy-associated immune dysfunction may thus create niches enabling normally low-pathogenic zoonotic viruses to persist, evolve, and acquire severe neurovirulence.
Source: Acta Neuropathologica
Authors: Christina Krueger, Christoph Schaefers, Thomas Guenther, Lisa Leypoldt, Ricardo Ahrens, Winfried Alsdorf, Maximilian Al-Bazaz, Katja Weisel, Sofie-Katrin Kadel, Leo Rasche, Niels Weinhold, Marc Raab, Julia Hoppe, Alexander Postel, Denise Heim, Kerstin Reumann, Alexis Robitaille, Patrick Bluemke, Felix Fischbach, Eckhard Schlemm, Manuel Friese, Tim Magnus, Axel Nierhaus, Stefan Kluge, Benjamin Ondruschka, Catena Kresbach, Matthias Dottermusch, Marc Luetgehetmann, Nicole Fischer, Adam Grundhoff
Language: English
Topic: Virology and Viral Diseases
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
OpenAlex ID: W7225777181