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Journal of Virology, January 2001, p. 11-18, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.11-18.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Vaccinia Virus Vectors with an Inactivated Gamma Interferon Receptor Homolog Gene (B8R) Are Attenuated In Vivo without a Concomitant Reduction in Immunogenicity

Paulo H. Verardi, Leslie A. Jones, Fatema H. Aziz, Shabbir Ahmad, and Tilahun D. Yilma*

International Laboratory of Molecular Biology for Tropical Disease Agents, Department of Veterinary Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California 95616

Received 23 August 2000/Accepted 3 October 2000

The vaccinia virus (VV) B8R gene encodes a secreted protein with homology to the gamma interferon (IFN-gamma ) receptor. In vitro, the B8R protein binds to and neutralizes the antiviral activity of several species of IFN-gamma , including human and rat IFN-gamma ; it does not, however, bind significantly to murine IFN-gamma . Here we report on the construction and characterization of recombinant VVs (rVVs) lacking the B8R gene. While the deletion of this gene had no effect on virus replication in vitro, rVVs lacking the B8R gene were attenuated for mice. There was a significant decrease in weight loss and mortality in normal mice, and nude mice survived significantly longer than did controls inoculated with parental virus. This is a surprising result considering the minimal binding of the B8R protein to murine IFN-gamma and its failure to block the antiviral activity of this cytokine in vitro. Such reduction in virulence could not be determined in rats, since they are considerably more resistant to VV infection than are mice. Finally, deletion of the B8R gene had no detectable effects on humoral immune responses. Mice and rats vaccinated with the rVVs showed identical humoral responses to both homologous and heterologous genes expressed by VV. This study demonstrates that the deletion of the VV B8R gene leads to enhanced safety without a concomitant reduction in immunogenicity.

* Corresponding author. Mailing address: International Laboratory of Molecular Biology for Tropical Disease Agents, Department of Veterinary Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616. Phone: (530) 752-8306. Fax: (530) 752-1354. E-mail: tdyilma{at}ucdavis.edu.

Journal of Virology, January 2001, p. 11-18, Vol. 75, No. 1
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.1.11-18.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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