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Journal of Virology, January 2001, p. 850-856, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.850-856.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Both Carboxy- and Amino-Terminal Domains of the Vaccinia Virus Interferon Resistance Gene, E3L, Are Required for Pathogenesis in a Mouse Model

Teresa A. Brandt and Bertram L. Jacobs*

Department of Microbiology, Graduate Program in Molecular and Cellular Biology, Arizona State University, Tempe, Arizona 85287-2701

Received 16 August 2000/Accepted 10 October 2000

The vaccinia virus (VV) E3L gene is responsible for providing interferon (IFN) resistance and a broad host range to VV in cell culture. The E3L gene product contains two distinct domains. A conserved carboxy-terminal domain, which is required for the IFN resistance and broad host range of the virus, has been shown to bind double-stranded RNA (dsRNA) and inhibit the antiviral dsRNA-dependent protein kinase, PKR. The amino-terminal domain, while conserved among orthopoxviruses, is dispensable in cell culture. To study the role of E3L in whole-animal infections, WR strain VV recombinants either lacking E3L (VVDelta E3L) or expressing an amino-terminal (VVE3LDelta 83N) or carboxy-terminal (VVE3LDelta 26C) truncation of E3L were constructed. Whereas wild-type VV had a 50% lethal dose of approximately 104 PFU after intranasal infection, and elicited severe weight loss and morbidity, VVDelta E3L was apathogenic, leading to no death, weight loss, or morbidity. VVDelta E3L was also apathogenic after intracranial injection. Although the amino-terminal domain of E3L is dispensable for infection of cells in culture, both the amino- and carboxy-terminal domains of E3L were required for full pathogenesis in intranasal infections. These results demonstrate that the entire E3L gene is required for pathogenesis in the mouse model.

* Corresponding author. Mailing address: Department of Microbiology, Graduate Program in Molecular and Cellular Biology, Arizona State University, Tempe, AZ 85287-2701. Phone: (480) 965-1457. Fax: (480) 965-0098. E-mail: bjacobs{at}asu.edu.

Journal of Virology, January 2001, p. 850-856, Vol. 75, No. 2
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.2.850-856.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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