Proteomic screening of variola virus reveals a unique NF-κB inhibitor that is highly conserved among pathogenic orthopoxviruses

Mohamed R. Mohamed, Masmudur M. Rahman, Jerry S. Lanchbury, Donna Shattuck, Chris Neff, Max Dufford, Nick Van Buuren, Katharine Fagan, Michele Barry, Scott Smith, Inger Damon, Grant McFadden

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Identification of the binary interactions between viral and host proteins has become a valuable tool for investigating viral tropism and pathogenesis. Here, we present the first systematic protein interaction screening of the unique variola virus proteome by using yeast 2-hybrid screening against a variety of human cDNA libraries. Several protein-protein interactions were identified, including an interaction between variola G1R, an ankryin/F-box containing protein, and human nuclear factor kappa-B1 (NF-κB1)/p105. This represents the first direct interaction between a pathogen-encoded protein and NF-κB1/p105. Orthologs of G1R are present in a variety of pathogenic orthopoxviruses, but not in vaccinia virus, and expression of any one of these viral proteins blocks NF-κB signaling in human cells. Thus, proteomic screening of variola virus has the potential to uncover modulators of the human innate antiviral responses.

Original languageEnglish (US)
Pages (from-to)9045-9050
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number22
DOIs
StatePublished - Jun 2 2009
Externally publishedYes

Keywords

  • Ankyrin repeats
  • Skp1
  • Yeast 2-hybrid

ASJC Scopus subject areas

  • General

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