Measles-like hypermutation of a Newcastle disease virus drives fatal encephalitis during BCMA × CD3 T-cell-redirecting immunotherapy.
Christina Krueger, Christoph Schaefers, Thomas Guenther et al.
✦ AI-curated · Sources linked
Case in brief
A patient with multiple myeloma receiving maintenance teclistamab, daratumumab, and lenalidomide developed rapidly progressive brainstem-cerebellar encephalitis. Conventional microbiological tests were negative, but metagenomic RNA sequencing of a cerebellar biopsy detected abundant Newcastle disease virus (AOaV-1). Viral analysis showed extensive A-to-G and U-to-C substitutions concentrated in the matrix gene, with two distinct hypermutated CNS haplotypes. Post-mortem testing found widespread brain involvement and further viral diversification; urine contained a minimally mutated putative ancestral lineage. The findings supported peripheral infection followed by CNS seeding and compartmentalized evolution. The encephalitis was fatal.
What made this case unusual
A typically mild human infection showed selective matrix-gene hypermutation resembling persistent measles virus infection in subacute sclerosing panencephalitis, alongside two independently hypermutated CNS haplotypes and a minimally mutated putative ancestral lineage in urine.
Diagnostic / clinical pearl
When conventional testing is negative in rapidly progressive encephalitis, unbiased metagenomic sequencing of affected brain tissue may identify an unexpected neuroinvasive pathogen.
Why it matters
The case supports the possibility that profound immunotherapy-associated immune dysfunction can permit a normally low-pathogenic zoonotic virus to persist and diversify within the CNS.