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Journal of Virology, April 2005, p. 5105-5115, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5105-5115.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Expression of the Full-Length Form of gp2 of Equine Herpesvirus 1 (EHV-1) Completely Restores Respiratory Virulence to the Attenuated EHV-1 Strain KyA in CBA Mice

Patrick M. Smith,1* Shannon M. Kahan,1 Colin B. Rorex,1 Jens von Einem,2 Nikolaus Osterrieder,2 and Dennis J. O'Callaghan1

Center for Molecular and Tumor Virology and Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana,1 Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York2

Received 12 October 2004/ Accepted 24 November 2004

Wild-type equine herpesvirus 1 (EHV-1) strains express a large (250-kDa) glycoprotein, gp2, that is encoded by EUs4 (gene 71) located within the unique short region of the genome. DNA sequence analysis revealed that EUs4 of the pathogenic EHV-1 strain RacL11 is an open reading frame of 2,376 bp that encodes a protein of 791 amino acids. The attenuated EHV-1 vaccine strain KyA harbors an in-frame deletion of 1,242 bp from bp 222 to 1461 and expresses a truncated gp2 of 383 amino acids. To determine the relative contribution of gp2 to EHV-1 pathogenesis, we compared the course of respiratory infection of CBA mice infected with either wild-type RacL11, attenuated KyA, or a recombinant KyA that expresses the full-length gp2 protein (KyARgp2F). Mice infected with KyA lost a negligible amount of body weight (0.18% total weight loss) on day 1 postinfection and regained weight thereafter, whereas mice infected with KyARgp2F or RacL11 steadily lost weight beginning on day 1 and experienced a 20 and 18% loss in body weight, respectively, by day 3. Immunohistochemical and flow cytometric analyses revealed higher numbers of T and B lymphocytes and an extensive consolidation consisting of large numbers of Mac-1-positive cells in the lungs of animals infected with KyARgp2F compared to animals infected with KyA. RNase protection analyses revealed increased expression of numerous cytokines and chemokines, including interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor alpha, macrophage inflammatory protein 1{alpha} (MIP-1{alpha}), MIP-1ß, MIP-2, interferon {gamma}-inducible protein, monocyte chemotactic protein 1, and T-cell activation gene 3 at 12 h postinfection with KyARgp2F. Three independent DNA array experiments confirmed these results and showed a 2- to 13-fold increase in the expression of 31 inflammatory genes at 8 and 12 h postinfection with KyARgp2F compared to infection with KyA. Taken together, the results indicate that expression of full-length gp2 is sufficient to restore full respiratory virulence to the attenuated KyA strain and raise caution concerning the inclusion of full-length gp2 in the development of EHV-1 vaccines.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130. Phone: (318) 675-6706. Fax: (318) 675-5764. E-mail: psmith{at}lsuhsc.edu.

Journal of Virology, April 2005, p. 5105-5115, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.5105-5115.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dry, I., Haig, D. M., Inglis, N. F., Imrie, L., Stewart, J. P., Russell, G. C. (2008). Proteomic Analysis of Pathogenic and Attenuated Alcelaphine Herpesvirus 1. J. Virol. 82: 5390-5397 [Abstract] [Full Text]  
  • Van de Walle, G. R., Sakamoto, K., Osterrieder, N. (2008). CCL3 and Viral Chemokine-Binding Protein gG Modulate Pulmonary Inflammation and Virus Replication during Equine Herpesvirus 1 Infection. J. Virol. 82: 1714-1722 [Abstract] [Full Text]  


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