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Journal of Virology, April 2001, p. 3268-3276, Vol. 75, No. 7
Laboratoire des Lyssavirus, Department of
Virology, Institut Pasteur, Paris, France
Received 1 September 2000/Accepted 4 January 2001
The genetic diversity of representative members of the
Lyssavirus genus (rabies and rabies-related viruses) was
evaluated using the gene encoding the transmembrane
glycoprotein involved in the virus-host interaction,
immunogenicity, and pathogenicity. Phylogenetic analysis distinguished
seven genotypes, which could be divided into two major phylogroups
having the highest bootstrap values. Phylogroup I comprises the
worldwide genotype 1 (classic Rabies virus), the
European bat lyssavirus (EBL) genotypes 5 (EBL1) and 6 (EBL2), the African genotype 4 (Duvenhage virus), and the Australian bat lyssavirus genotype 7. Phylogroup II
comprises the divergent African genotypes 2 (Lagos bat
virus) and 3 (Mokola virus). We studied immunogenic
and pathogenic properties to investigate the biological significance of
this phylogenetic grouping. Viruses from phylogroup I (Rabies
virus and EBL1) were found to be pathogenic for mice when
injected by the intracerebral or the intramuscular route, whereas
viruses from phylogroup II (Mokola and Lagos bat viruses) were only
pathogenic by the intracerebral route. We showed that the
glycoprotein R333 residue essential for virulence was naturally replaced by a D333 in the phylogroup II viruses, likely resulting in their attenuated pathogenicity. Moreover,
cross-neutralization distinguished the same phylogroups. Within each
phylogroup, the amino acid sequence of the glycoprotein
ectodomain was at least 74% identical, and
antiglycoprotein virus-neutralizing antibodies displayed
cross-neutralization. Between phylogroups, the identity was less than
64.5% and the cross-neutralization was absent, explaining why the
classical rabies vaccines (phylogroup I) cannot protect against
lyssaviruses from phylogroup II. Our tree-axial analysis divided
lyssaviruses into two phylogroups that more closely reflect their
biological characteristics than previous serotypes and genotypes.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.7.3268-3276.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Evidence of Two Lyssavirus Phylogroups
with Distinct Pathogenicity and Immunogenicity
*
Corresponding author. Mailing address: Laboratoire des
Lyssavirus, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: (33) 1-40613134. Fax: (33) 1-40613256. E-mail: ntordo{at}pasteur.fr.
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