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Journal of Virology, February 2003, p. 1784-1792, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.1784-1792.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Core 2 ß-1,6-N-Acetylglucosaminyltransferase-Mucin Encoded by Bovine Herpesvirus 4 Was Acquired from an Ancestor of the African Buffalo

N. Markine-Goriaynoff,1 J.-P. Georgin,1 M. Goltz,2 W. Zimmermann,2 H. Broll,2 H. M. Wamwayi,3 P.-P. Pastoret,1 P. M. Sharp,4 and A. Vanderplasschen1*

Immunology-Vaccinology, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium,1 P24/Xenotransplantation, Robert Koch-Institut, 13353 Berlin, Germany,2 National Veterinary Research Centre, Kikuyu, Kenya,3 Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, United Kingdom4

Received 6 September 2002/ Accepted 31 October 2002

The Bo17 gene of bovine herpesvirus 4 (BoHV-4) is the only viral gene known to date that encodes a homologue of the cellular core 2 ß-1,6-N-acetylglucosaminyltransferase-mucin type (C2GnT-M). To investigate the origin and evolution of the Bo17 gene, we analyzed its distribution among BoHV-4 strains and determined the sequences of Bo17 from nine representative strains and of the C2GnT-M gene from six species of ruminants expected to encompass the group within which the gene acquisition occurred. Of 34 strains of BoHV-4, isolated from four different continents, all were found to contain the Bo17 gene. Phylogenetic analyses indicated that Bo17 was acquired from a recent ancestor of the African buffalo, implying that cattle subsequently acquired BoHV-4 by cross-species transmission. The rate of synonymous nucleotide substitution in Bo17 was estimated at 5 x 10-8 to 6 x 10-8 substitutions/site/year, consistent with previous estimates made under the assumption that herpesviruses have cospeciated with their hosts. The Bo17 gene acquisition was dated to around 1.5 million years ago. Bo17 sequences from BoHV-4 strains from African buffalo and from cattle formed two separate clades, estimated to have split about 700,000 years ago. Analysis of the ratio of nonsynonymous to synonymous nucleotide substitutions revealed a burst of amino acid replacements subsequent to the transfer of the cellular gene to the viral genome, followed by a return to a strong constraint on nonsynonymous changes during the divergence of contemporary BoHV-4 strains. The Bo17 gene represents the most recent of the known herpesvirus gene acquisitions and provides the best opportunity for learning more about this important process of viral evolution.

* Corresponding author. Mailing address: Immunology-Vaccinology (B43 b), Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium. Phone: 32-4-3664264. Fax: 32-4-3663908. E-mail: A.vdplasschen{at}ulg.ac.be.

Journal of Virology, February 2003, p. 1784-1792, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.1784-1792.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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