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-DeltaM) from cDNA. In comparison with standard MV, MV-DeltaM was considerably more efficient at inducing cell-to-cell fusion but virus titres were reduced approximately 250-fold. In MV-DeltaM-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-DeltaM or with another highly fusogenic virus bearing glycoproteins with shortened cytoplasmic tails (MV-Delta(tails)). MV-DeltaM 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.
Institut für Molekularbiologie, Abt. I, Universität Zürich, Hönggerberg, 8093 Zürich, Switzerland.
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T
Cathomen
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B
Mrkic
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D
Spehner
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R
Drillien
R
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Naef
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J
Pavlovic
A
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Aguzzi
M A
MA
Billeter
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Cattaneo
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001921:Brain / Q000473:pathology / Q000821:virology*; D002459:Cell Fusion / Q000502:physiology*; D002522:Chlorocebus aethiops; D016679:Genome, Viral; D015726:Giant Cells; D008459:Measles virus / Q000472:pathogenicity* / Q000502:physiology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000502:physiology; D013344:Subacute Sclerosing Panencephalitis / Q000473:pathology / Q000821:virology*; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000502:physiology*; D015678:Viral Structural Proteins / Q000032:analysis; D014779:Virus Replication
D015703:Antigens, CD; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D014763:Viral Matrix Proteins; D015678:Viral Structural Proteins