Proteomic screening of variola virus reveals a unique NF-kappaB inhibitor that is highly conserved among pathogenic orthopoxviruses.
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.
Mohamed
Mohamed R
MR
Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Rahman
Masmudur M
MM
Lanchbury
Jerry S
JS
Shattuck
Donna
D
Neff
Chris
C
Dufford
Max
M
van Buuren
Nick
N
Fagan
Katharine
K
Barry
Michele
M
Smith
Scott
S
Damon
Inger
I
McFadden
Grant
G
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*
D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D014764:Viral Proteins