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Journal of Virology, November 2000, p. 10714-10728, Vol. 74, No. 22
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Evolution of Bovine Respiratory Syncytial Virus

Jean-François Valarcher,1,2 François Schelcher,1 and Hervé Bourhy2,*

UMR INRA-ENVT de Physiopathologie Infectieuse et Parasitaire des Ruminants, ENVT, 31076 Toulouse Cedex 3,1 and Unité de la Rage, Institut Pasteur, 75724 Paris Cedex 15,2 France

Received 28 March 2000/Accepted 26 July 2000

Until now, the analysis of the genetic diversity of bovine respiratory syncytial virus (BRSV) has been based on small numbers of field isolates. In this report, we determined the nucleotide and deduced amino acid sequences of regions of the nucleoprotein (N protein), fusion protein (F protein), and glycoprotein (G protein) of 54 European and North American isolates and compared them with the sequences of 33 isolates of BRSV obtained from the databases, together with those of 2 human respiratory syncytial viruses and 1 ovine respiratory syncytial virus. A clustering of BRSV sequences according to geographical origin was observed. We also set out to show that a continuous evolution of the sequences of the N, G, and F proteins of BRSV has been occurring in isolates since 1967 in countries where vaccination was widely used. The exertion of a strong positive selective pressure on the mucin-like region of the G protein and on particular sites of the N and F proteins is also demonstrated. Furthermore, mutations which are located in the conserved central hydrophobic part of the ectodomain of the G protein and which result in the loss of four Cys residues and in the suppression of two disulfide bridges and an alpha  helix critical to the three-dimensional structure of the G protein have been detected in some recent French BRSV isolates. This conserved central region, which is immunodominant in BRSV G protein, thus has been modified in recent isolates. This work demonstrates that the evolution of BRSV should be taken into account in the rational development of future vaccines.

* Corresponding author. Mailing address: Unité de la Rage, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: 33.1.45.68.87.85. Fax: 33.1.40.61.30.20. E-mail: hbourhy{at}pasteur.fr.

Journal of Virology, November 2000, p. 10714-10728, Vol. 74, No. 22
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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