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

doi:10.1128/JVI.75.2.850-856.2001

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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 incell culture. The E3L gene product contains two distinct domains.A conserved carboxy-terminal domain, which is required for theIFN resistance and broad host range of the virus, has been shownto bind double-stranded RNA (dsRNA) and inhibit the antiviraldsRNA-dependent protein kinase, PKR. The amino-terminal domain,while conserved among orthopoxviruses, is dispensable in cellculture. To study the role of E3L in whole-animal infections,WR strain VV recombinants either lacking E3L (VV $Delta$ E3L) or expressingan amino-terminal (VVE3L $Delta$ 83N) or carboxy-terminal (VVE3L $Delta$ 26C)truncation of E3L were constructed. Whereas wild-type VV had a50% lethal dose of approximately 10⁴ PFU after intranasal infection, and elicited severe weight lossand morbidity, VV $Delta$ E3L was apathogenic, leading to no death, weightloss, or morbidity. VV $Delta$ E3L was also apathogenic after intracranialinjection. Although the amino-terminal domain of E3L is dispensablefor infection of cells in culture, both the amino- and carboxy-terminaldomains of E3L were required for full pathogenesis in intranasalinfections. These results demonstrate that the entire E3L geneis required for pathogenesis in the mousemodel.

^* Corresponding author. Mailing address: Department of Microbiology, Graduate Program in Molecular and Cellular Biology, ArizonaState 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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