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

 Previous Article  |  Next Article 

Journal of Virology, March 2004, p. 2336-2347, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2336-2347.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Investigation of the Susceptibility of Human Cell Lines to Bovine Herpesvirus 4 Infection: Demonstration that Human Cells Can Support a Nonpermissive Persistent Infection Which Protects Them against Tumor Necrosis Factor Alpha-Induced Apoptosis

L. Gillet,1 F. Minner,1 B. Detry,1 F. Farnir,2 L. Willems,3 M. Lambot,1 E. Thiry,1 P.-P. Pastoret,4 F. Schynts,1 and A. Vanderplasschen1*

Immunology-Vaccinology,1 Biostatistics, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège,2 Faculty of Agronomy, B-5030 Gembloux, Belgium,3 Compton Laboratory, Institute for Animal Health, Compton, Newbury, Berks RG20 7NN, United Kingdom4

Received 20 August 2003/ Returned for modification 14 October 2003/ Accepted 29 October 2003

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus that has a worldwide distribution in the population of cattle. Many factors make human contamination by BoHV-4 likely to occur. In this study, we performed in vitro experiments to assess the risk and the consequences of human infection by BoHV-4. First, by using a recombinant BoHV-4 strain expressing enhanced green fluorescent protein under the control of the human cytomegalovirus immediate-early gene promoter, we tested 21 human cell lines for their sensitivity and their permissiveness to BoHV-4 infection. These experiments revealed that human cell lines from lymphoid and myeloid origins were resistant to infection, whereas epithelial cells, carcinoma cells, or adenocarcinoma cells isolated from various organs were sensitive but poorly permissive to BoHV-4 infection. Second, by using the HeLa cell line as a model of human cells sensitive but not permissive to BoHV-4 infection, we investigated the resistance of infected cells to apoptosis and the persistence of the infection through cellular divisions. The results obtained can be summarized as follows. (i) BoHV-4 nonpermissive infection of HeLa cells protects them against tumor necrosis factor alpha-induced apoptosis. (ii) BoHV-4 infection of HeLa cells persists in cell culture; however, the percentage of infected cells decreases with time due to erratic transmission of the viral genome through cell division. (iii) BoHV-4 infection has no effect on the rate of HeLa cell division. Altogether, these data suggest that BoHV-4 could infect humans. This study also stresses the importance of considering the insidious effects of nonpermissive infection when the biosafety of animal gammaherpesviruses for humans is being considered.


* Corresponding author. Mailing address: Immunology-Vaccinology (B43b), Department of Infectious and Parasitic Diseases, 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, March 2004, p. 2336-2347, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2336-2347.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Donofrio, G., Herath, S., Sartori, C., Cavirani, S., Flammini, C. F., Sheldon, I. M. (2007). Bovine herpesvirus 4 is tropic for bovine endometrial cells and modulates endocrine function. Reproduction 134: 183-197 [Abstract] [Full Text]  
  • Dewals, B., Thirion, M., Markine-Goriaynoff, N., Gillet, L., de Fays, K., Minner, F., Daix, V., Sharp, P. M., Vanderplasschen, A. (2006). Evolution of Bovine herpesvirus 4: recombination and transmission between African buffalo and cattle. J. Gen. Virol. 87: 1509-1519 [Abstract] [Full Text]  
  • Gillet, L., Dewals, B., Farnir, F., de Leval, L., Vanderplasschen, A. (2005). Bovine Herpesvirus 4 Induces Apoptosis of Human Carcinoma Cell Lines In vitro and In vivo. Cancer Res. 65: 9463-9472 [Abstract] [Full Text]  
  • Bona, C., Dewals, B., Wiggers, L., Coudijzer, K., Vanderplasschen, A., Gillet, L. (2005). Short Communication: Pasteurization of Milk Abolishes Bovine Herpesvirus 4 Infectivity. J DAIRY SCI 88: 3079-3083 [Abstract] [Full Text]  
  • Gillet, L., Daix, V., Donofrio, G., Wagner, M., Koszinowski, U. H., China, B., Ackermann, M., Markine-Goriaynoff, N., Vanderplasschen, A. (2005). Development of bovine herpesvirus 4 as an expression vector using bacterial artificial chromosome cloning. J. Gen. Virol. 86: 907-917 [Abstract] [Full Text]