A role for Z-DNA binding in vaccinia virus pathogenesis

Yang Gyun Kim, Maneesha Muralinath, Teresa Brandt, Matthew Pearcy, Kevin Hauns, Ky Lowenhaupt, Bertram Jacobs, Alexander Rich

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

The N-terminal domain of the E3L protein of vaccinia virus has sequence similarity to a family of Z-DNA binding proteins of defined three-dimensional structure and it is necessary for pathogenicity in mice. When other Z-DNA-binding domains are substituted for the similar E3L domain, the virus retains its lethality after intracranial inoculation. Mutations decreasing Z-DNA binding in the chimera correlate with decreases in viral pathogenicity, as do analogous mutations in wild-type E3L. A chimeric virus incorporating a related protein that does not bind Z-DNA is not pathogenic, but a mutation that creates Z-DNA binding makes a lethal virus. The ability to bind the Z conformation is thus essential to E3L activity. This finding may allow the design of a class of antiviral agents, including agents against variola (smallpox), which has an almost identical E3L.

Original languageEnglish (US)
Pages (from-to)6974-6979
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number12
DOIs
StatePublished - Jun 10 2003

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Z-Form DNA
Vaccinia virus
Smallpox
Viruses
Mutation
Virulence
DNA-Binding Proteins
Antiviral Agents
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Kim, Y. G., Muralinath, M., Brandt, T., Pearcy, M., Hauns, K., Lowenhaupt, K., ... Rich, A. (2003). A role for Z-DNA binding in vaccinia virus pathogenesis. Proceedings of the National Academy of Sciences of the United States of America, 100(12), 6974-6979. https://doi.org/10.1073/pnas.0431131100

A role for Z-DNA binding in vaccinia virus pathogenesis. / Kim, Yang Gyun; Muralinath, Maneesha; Brandt, Teresa; Pearcy, Matthew; Hauns, Kevin; Lowenhaupt, Ky; Jacobs, Bertram; Rich, Alexander.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 12, 10.06.2003, p. 6974-6979.

Research output: Contribution to journalArticle

Kim, YG, Muralinath, M, Brandt, T, Pearcy, M, Hauns, K, Lowenhaupt, K, Jacobs, B & Rich, A 2003, 'A role for Z-DNA binding in vaccinia virus pathogenesis', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 12, pp. 6974-6979. https://doi.org/10.1073/pnas.0431131100
Kim, Yang Gyun ; Muralinath, Maneesha ; Brandt, Teresa ; Pearcy, Matthew ; Hauns, Kevin ; Lowenhaupt, Ky ; Jacobs, Bertram ; Rich, Alexander. / A role for Z-DNA binding in vaccinia virus pathogenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 12. pp. 6974-6979.
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