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J. Virol., 01 1998, 273-278, Vol 72, No. 1
P Coulon, JP Ternaux, A Flamand and C Tuffereau
An antigenic double mutant of rabies virus (challenge virus standard [CVS]
strain) was selected by successive use of two neutralizing antiglycoprotein
monoclonal antibodies, both specific for antigenic site III. This mutant
differed from the original virus strain by two amino acid substitutions in
the ectodomain of the glycoprotein. The lysine in position 330 and the
arginine in position 333 were replaced by asparagine and methionine,
respectively. This double mutant was not pathogenic for adult mice. When
injected intramuscularly into the forelimbs of adult mice, this virus could
not penetrate the nervous system, either by the motor or by the sensory
route, while respective single mutants infected motoneurons in the spinal
cord and sensory neurons in the dorsal root ganglia. In vitro experiments
showed that the double mutant was able to infect BHK cells, neuroblastoma
cells, and freshly prepared embryonic motoneurons, albeit with a lower
efficiency than the CVS strain. Upon further incubation at 37 degrees C,
the motoneurons became resistant to infection by the mutant while remaining
permissive to CVS infection. These results suggest that rabies virus uses
different types of receptors: a molecule which is ubiquitously expressed at
the surface of continuous cell lines and which is recognized by both CVS
and the double mutant and a neuron- specific molecule which is not
recognized by the double mutant.
Copyright © 1998, American Society for Microbiology
An avirulent mutant of rabies virus is unable to infect motoneurons in vivo and in vitro
Laboratoire de Genetique des Virus, Centre National de la Recherche Scientifique, Gif sur Yvette, France.
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