Recombinant rabies virus compositions

Abstract

Recombinant rabies viruses in which the arginine residue of the glycoprotein (G) at amino acid position 333 is exchanged, renders these viruses nonpathogenic for immunocompetent mammals regardless of the route of infection. Some of these recombinant rabies viruses after several serial virus passages in newborn mice can become pathogenic for adult mice. The reversion to the pathogenic phenotype is associated with a thymidine to adenosine mutation (T→A) at position 639 of the G gene, which results in an asparagine to lysine exchange at position 194 of G. The codon at position 637-639 was changed by site directed mutagenesis to replace asparagine at position 194 by an amino acid that minimized the possibility for an Asn→Lys exchange at amino acid position 194 of G and prevents reversion to a pathogenic form of the virus.

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