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 MV-less MV (MV-ΔM) from cDNA. In comparison with standard MV, MV-ΔM was considerably more efficient at inducing cell-to-cell fusion but virus titres were reduced ~ 250-fold. In MV-ΔM-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-ΔM or with another highly fusogenic virus bearing glycoproteins with shortened cytoplasmic tails (MV-Δ(tails)). MV-ΔM and MV-Δ(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.