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A matrix‐less measles virus is infectious and elicits extensive cell fusion: consequences for propagation in the brain
Author(s) -
Cathomen Toni,
Mrkic Branka,
Spehner Danièle,
Drillien Robert,
Naef Roland,
Pavlovic Jovan,
Aguzzi Adriano,
Billeter Martin A.,
Cattaneo Roberto
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.14.3899
Subject(s) - measles virus , subacute sclerosing panencephalitis , biology , virology , glycoprotein , virus , viral matrix protein , paramyxoviridae , cytoplasm , cell fusion , complementary dna , syncytium , fusion protein , cell culture , microbiology and biotechnology , measles , genetics , recombinant dna , gene , viral disease , vaccination
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‐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.