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Evidence that vaccinia virulence factor E3L binds to Z-DNA in vivo : Implications for development of a therapy for poxvirus infection
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
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| Personen und Körperschaften: | , , , , |
| In: | Proceedings of the National Academy of Sciences, 101, 2004, 6, S. 1514-1518 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| Zusammenfassung: | <jats:p> The E3L gene product found in all poxviruses is required for the lethality of mice in vaccinia virus infection. Both the C-terminal region, consisting of a double-stranded RNA-binding motif, and the N-terminal region (vZ <jats:sub>E3L</jats:sub> ), which is similar to the Zα family of Z-DNA-binding proteins, are required for infection. It has recently been demonstrated that the function of the N-terminal domain depends on its ability to bind Z-DNA; Z-DNA-binding domains from unrelated mammalian proteins fully complement an N-terminal deletion of E3L. Mutations that decrease affinity for Z-DNA have similar effects in decreasing pathogenicity. Compounds that block the Z-DNA-binding activity of E3L may also limit infection by the poxvirus. Here we show both an <jats:italic>in vitro</jats:italic> and an <jats:italic>in vivo</jats:italic> assay with the potential to be used in screening for such compounds. Using a conformation-specific yeast one-hybrid assay, we compared the results for Z-DNA binding of vZ <jats:sub>E3L</jats:sub> with those for human Zβ <jats:sub>ADAR1</jats:sub> , a peptide that has similarity to the Zα motif but does not bind Z-DNA, and with a mutant of hZβ <jats:sub>ADAR1</jats:sub> , which binds Z-DNA. The results suggest that this system can be used for high-throughput screening. </jats:p> |
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| Umfang: | 1514-1518 |
| ISSN: |
0027-8424
1091-6490 |
| DOI: | 10.1073/pnas.0308260100 |