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Journal of Virology, January 1999, p. 791-796, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Down Regulation of Gene Expression by the Vaccinia Virus D10 Protein

Teri Shors,dagger James G. Keck,Dagger and Bernard Moss*

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0445

Received 10 August 1998/Accepted 15 October 1998

Vaccinia virus genes are expressed in a sequential fashion, suggesting a role for negative as well as positive regulatory mechanisms. A potential down regulator of gene expression was mapped by transfection assays to vaccinia virus open reading frame D10, which encodes a protein with no previously known function. Inhibition was independent of the promoter type used for the reporter gene, indicating that the mechanism did not involve promoter sequence recognition. The inhibition was overcome, however, when the open reading frame of the reporter gene was preceded by the encephalomyocarditis virus internal ribosome entry site, which excludes the possibility of nonspecific metabolic or other antiviral effects and suggests that capped mRNAs or cap-dependent translation might be the target of the D10 product. The inducible overexpression of the D10 gene by a recombinant vaccinia virus severely inhibited viral protein synthesis, decreased the steady-state level of viral late mRNA, and blocked the formation of infectious virus.

* Corresponding author. Mailing address: Building 4, Room 229, 4 Center Dr., MSC 0445, National Institutes of Health, Bethesda, MD 20892-0445. Phone: (301) 496-9869. Fax: (301) 480-1147. E-mail: bmoss{at}nih.gov.

dagger Present address: Department of Biology and Microbiology, University of Wisconsin Oshkosh, Oshkosh, WI 54901-8640.

Dagger Present address: Strata Biosciences, Alameda, CA 94501.

Journal of Virology, January 1999, p. 791-796, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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