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Journal of Virology, September 2001, p. 8096-8104, Vol. 75, No. 17
Laboratoire des Lyssavirus, Department of
Virology, Institut Pasteur, Paris, France
Received 26 March 2001/Accepted 5 June 2001
Lyssaviruses are unsegmented RNA viruses causing rabies. Their
vectors belong to the Carnivora and Chiroptera orders. We studied 36 carnivoran and 17 chiropteran lyssaviruses representing the main
genotypes and variants. We compared their genes encoding the surface
glycoprotein, which is responsible for receptor recognition and
membrane fusion. The glycoprotein is the main protecting antigen and
bears virulence determinants. Point mutation is the main force in
lyssavirus evolution, as Sawyer's test and phylogenetic analysis showed no evidence of recombination. Tests of neutrality indicated a
neutral model of evolution, also supported by globally high ratios of
synonymous substitutions (dS) to
nonsynonymous substitutions (dN)
(>7). Relative-rate tests suggested similar rates of evolution for all
lyssavirus lineages. Therefore, the absence of recombination and
similar evolutionary rates make phylogeny-based conclusions reliable.
Phylogenetic reconstruction strongly supported the hypothesis that host
switching occurred in the history of lyssaviruses. Indeed, lyssaviruses
evolved in chiropters long before the emergence of carnivoran rabies,
very likely following spillovers from bats. Using dated isolates, the
average rate of evolution was estimated to be roughly 4.3 × 10
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.17.8096-8104.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Host Switching in Lyssavirus History
from the Chiroptera to the Carnivora Orders
4 dS/site/year.
Consequently, the emergence of carnivoran rabies from chiropteran
lyssaviruses was determined to have occurred 888 to 1,459 years ago.
Glycoprotein segments accumulating more dN
than dS were distinctly detected in
carnivoran and chiropteran lyssaviruses. They may have contributed to
the adaptation of the virus to the two distinct mammal orders. In
carnivoran lyssaviruses they overlapped the main antigenic sites, II
and III, whereas in chiropteran lyssaviruses they were located in
regions of unknown functions.
*
Corresponding author. Mailing address: Institut
Pasteur, Laboratoire des Lyssavirus, 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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