A matrix-less measles virus is infectious and elicits extensive cell fusion: consequences for propagation in the brain

Measles viruses (MV) can be isolated from the brains of deceased subacute sclerosing panencephalitis patients only in a cell-associated form. These viruses are often defective in the matrix (M) protein and always seem to have an altered fusion protein cytoplasmic tail. We reconstituted a cell-free, infectious M-less MV (MV-Delta M) from cDNA, In comparison with standard MV, MV-Delta M was considerably more efficient at inducing cell-to-cell fusion but virus titres were reduced similar to 250-fold, In MV-Delta M-induced syncytia the ribonucleocapsids and glycoproteins largely lost co-localization, confirming the role of M protein as the virus assembly organizer, Genetically modified mice were inoculated with MV-Delta M or with another highly fusogenic virus bearing glycoproteins with shortened cytoplasmic tails (MV-Delta(tails)). MV-Delta M and MV-Delta(tails) lost acute pathogenicity but penetrated more deeply into the brain parenchyma than standard MV, We suggest that enhanced cell fusion may also favour the propagation of mutated, assembly-defective MV in human brains.