title: Proteomic screening of variola virus reveals a unique NF-kappaB inhibitor that is highly conserved among pathogenic orthopoxviruses.
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-kappaB1)/p105. This represents the first direct interaction between a pathogen-encoded protein and NF-kappaB1/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-kappaB signaling in human cells. Thus, proteomic screening of variola virus has the potential to uncover modulators of the human innate antiviral responses.
authors.affiliation: Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Mohamed
authors.forename: Masmudur M
authors.initials: MM
authors.lastname: Rahman
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Lanchbury
authors.forename: Donna
authors.initials: D
authors.lastname: Shattuck
authors.forename: Chris
authors.initials: C
authors.lastname: Neff
authors.forename: Max
authors.initials: M
authors.lastname: Dufford
authors.forename: Nick
authors.initials: N
authors.lastname: van Buuren
authors.forename: Katharine
authors.initials: K
authors.lastname: Fagan
authors.forename: Michele
authors.initials: M
authors.lastname: Barry
authors.forename: Scott
authors.initials: S
authors.lastname: Smith
authors.forename: Inger
authors.initials: I
authors.lastname: Damon
authors.forename: Grant
authors.initials: G
authors.lastname: McFadden
mesh_terms: D002460:Cell Line; D015723:Gene Library; D054884:Host-Pathogen Interactions; D006801:Humans; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018155:Orthopoxvirus / Q000378:metabolism / Q000472:pathogenicity; D040901:Proteomics; D020798:Two-Hybrid System Techniques; D012901:Variola virus / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D014764:Viral Proteins