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

153 Scopus citations

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

ASJC Scopus subject areas

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