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PMID: 11134298 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Both carboxy- and amino-terminal domains of the vaccinia virus interferon resistance gene, E3L, are required for pathogenesis in a mouse model.

Journal of virology ·Vol. 75 ·No. 2 ·2001-01-00 ·Pages 850-6

Brandt TA, Jacobs BL

Abstract

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 (VVDeltaE3L) or expressing an amino-terminal (VVE3LDelta83N) or carboxy-terminal (VVE3LDelta26C) truncation of E3L were constructed. Whereas wild-type VV had a 50% lethal dose of approximately 10(4) PFU after intranasal infection, and elicited severe weight loss and morbidity, VVDeltaE3L was apathogenic, leading to no death, weight loss, or morbidity. VVDeltaE3L 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.

MeSH Terms
Animals Brain/virology Disease Models, Animal Drug Resistance, Microbial Genes, Viral Humans Interferons/pharmacology Mice Mice, Inbred C57BL Protein Structure, Tertiary RNA-Binding Proteins/chemistry,genetics,metabolism Vaccinia/physiopathology,virology Vaccinia virus/genetics,pathogenicity Viral Proteins/chemistry,genetics,metabolism Virulence/genetics Virus Replication Weight Loss
Chemicals
E3L protein, Vaccinia virus RNA-Binding Proteins Viral Proteins Interferons
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Brandt T A
Department of Microbiology, Graduate Program in Molecular and Cellular Biology, Arizona State University, Tempe, Arizona 85287-2701, USA.
Jacobs B L
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.75.2.850-856.2001
Published
2001-01-00
Pages
850-6
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC113981
Subset
IM
Grants
NCI NIH HHS · CA48654 · United States
External Links
PubMed source DOI: 10.1128/JVI.75.2.850-856.2001 PMC Full Text View journal details
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