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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-
) receptor. In vitro, the
B8R protein binds to and neutralizes the antiviral activity of several
species of IFN-
, including human and rat IFN-
; it does not,
however, bind significantly to murine IFN-
. 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-
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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