This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Al-Mubarak, A. Articles by Chowdhury, S. I. Search for Related Content PubMed PubMed Citation Articles by Al-Mubarak, A. Articles by Chowdhury, S. I.

 Previous Article  |  Next Article 

Journal of Virology, May 2004, p. 4806-4816, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4806-4816.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A Glycine-Rich Bovine Herpesvirus 5 (BHV-5) gE-Specific Epitope within the Ectodomain Is Important for BHV-5 Neurovirulence

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506,¹ Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, Nebraska 68588²

Received 20 November 2003/ Accepted 9 January 2004

The bovine herpesvirus 5 (BHV-5) gE ectodomain contains a glycine-rich epitope coding region (gE5 epitope), residues 204 to 218, that is significantly different from the corresponding gE region of BHV-1. Deletion of the gE epitope significantly reduced the neurovirulence of BHV-5 in rabbits. Pulse-chase analyses revealed that the epitope-deleted and wild-type gE were synthesized as N-glycosylated endoglycosidase H-sensitive precursors with approximate molecular masses of 85 kDa and 86 kDa, respectively. Like the wild-type gE, epitope-deleted gE complexed with gI and was readily transported from the endoplasmic reticulum. Concomitantly, the epitope-deleted and wild-type gE acquired posttranslational modifications in the Golgi leading to an increased apparent molecular mass of 93-kDa (epitope-deleted gE) and 94-kDa (wild-type gE). The kinetics of mutant and wild-type gE processing were similar, and both mature proteins were resistant to endoglycosidase H but sensitive to glycopeptidase F. The gE epitope-deleted BHV-5 formed wild-type-sized plaques in MDBK cells, and the epitope-deleted gE was expressed on the cell surface. However, rabbits infected intranasally with gE epitope-deleted BHV-5 did not develop seizures, and only 20% of the infected rabbits showed mild neurological signs. The epitope-deleted virus replicated efficiently in the olfactory epithelium. However, within the brains of these rabbits there was a 10- to 20-fold reduction in infected neurons compared with the number of infected neurons within the brains of rabbits infected with the gE5 epitope-reverted and wild-type BHV-5. In comparison, 70 to 80% of the rabbits exhibited severe neurological signs when infected with the gE5 epitope-reverted and wild-type BHV-5. These results indicated that anterograde transport of the gE epitope-deleted virus from the olfactory receptor neurons to the olfactory bulb is defective and that, within the central nervous system, the gE5 epitope-coding region was required for expression of the full virulence potential of BHV-5.

Contribution 03-236-J, Kansas Agricultural Experiment Station.

This article has been cited by other articles:

• Liu, Z. F., Brum, M. C. S., Doster, A., Jones, C., Chowdhury, S. I. (2008). A Bovine Herpesvirus Type 1 Mutant Virus Specifying a Carboxyl-Terminal Truncation of Glycoprotein E Is Defective in Anterograde Neuronal Transport in Rabbits and Calves. J. Virol. 82: 7432-7442 [Abstract] [Full Text]  
• Brower, A., Homb, K. M., Bochsler, P., Porter, R., Woods, K., Ubl, S., Krueger, D., Cigel, F., Toohey-Kurth, K. (2008). Encephalitis in aborted bovine fetuses associated with Bovine herpesvirus 1 infection. jvdi 20: 297-303 [Abstract] [Full Text]  
• Chowdhury, S. I., Mahmood, S., Simon, J., Al-Mubarak, A., Zhou, Y. (2006). The Us9 Gene of Bovine Herpesvirus 1 (BHV-1) Effectively Complements a Us9-Null Strain of BHV-5 for Anterograde Transport, Neurovirulence, and Neuroinvasiveness in a Rabbit Model. J. Virol. 80: 4396-4405 [Abstract] [Full Text]