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Journal of Virology, April 2009, p. 3127-3137, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02474-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Coinfection with Two Closely Related Alphaherpesviruses Results in a Highly Diversified Recombination Mosaic Displaying Negative Genetic Interference {triangledown}

Benoît Muylkens,1 Frédéric Farnir,2 François Meurens,3 Frédéric Schynts,1,{dagger} Alain Vanderplasschen,1 Michel Georges,2 and Etienne Thiry1*

Department of Infectious and Parasitic Diseases, Virology and Immunology, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium,1 Department of Animal Production, Animal Genomics, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium,2 Institut National de la Recherche Agronomique, UR1282, Infectiologie Animale et Santé Publique, F-37380 Nouzilly (Tours), France3

Received 2 December 2008/ Accepted 8 January 2009

Phylogenetic studies of the emergence and spread of natural recombinants in herpesviruses infecting humans and animals have been reported recently. However, despite an ever-increasing amount of evidence of recombination in herpesvirus history, the recombination process and the consequences on the genetic diversity of the progeny remain poorly characterized. We addressed this issue by using multiple single-nucleotide polymorphisms (SNPs) differentiating the two subtypes of an alphaherpesvirus, bovine herpesvirus 1 (BoHV-1). Analysis of a large sample of progeny virions obtained in a single growth cycle of coinfected BoHV-1 strains provided a prospective investigation of the recombination dynamics by using SNPs as recombination markers. We found that the simultaneous infection with two closely related herpesviruses results in a highly diversified recombination mosaic. From the analysis of multiple recombinants arising in the progeny, we provide the first evidence of genetic interference influencing the recombination process in herpesviruses. In addition, we report striking differences in the levels of recombination frequency observed along the BoHV-1 genome. With particular emphasis on the genetic structure of a progeny virus population rising in vitro, our data show to which extent recombination participates to the genetic diversification of herpesviruses.

* Corresponding author. Mailing address: Department of Infectious and Parasitic Diseases, Laboratory of Virology, Faculty of Veterinary Medicine, University of Liège, Boulevard de Colonster 20, B43b, B-4000 Sart-Tilman, Liège, Belgium. Phone: (32) 4 366 42 50. Fax: (32) 4 366 42 61. E-mail: etienne.thiry{at}ulg.ac.be

{triangledown} Published ahead of print on 19 January 2009.

{dagger} Present address: Division of Virology, GlaxoSmithKline Biologicals, Rixensart, Belgium.

Journal of Virology, April 2009, p. 3127-3137, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02474-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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