Proteomic screening of variola virus reveals a unique NF-κB inhibitor that is highly conserved among pathogenic orthopoxviruses
Proteomic screening of variola virus reveals a unique NF-κB inhibitor that is highly conserved among pathogenic orthopoxviruses
复制标题
DOI：
10.1073/pnas.0900452106
复制
发表时间：
2009-06-02
影响因子：
11.1
通讯作者：
McFadden, Grant
中科院分区：
文献类型：
--
作者：
Mohamed, R. Mohamed;Rahman, Masmudur M.;McFadden, Grant
鉴定病毒与宿主蛋白质之间的二元相互作用已成为研究病毒嗜性和致病机制的重要工具。在这里，我们提出了第一个系统的蛋白质相互作用筛选独特的天花病毒蛋白质组，使用酵母双杂交筛选对各种人类cDNA文库。鉴定了几种蛋白质-蛋白质相互作用，包括天花G1 R（一种含有锚蛋白/F盒的蛋白质）与人核因子κ B1（NF-κ B1）/p105之间的相互作用。这代表了病原体编码的蛋白质和NF-κ B1/p105之间的第一次直接相互作用。G1 R的直系同源物存在于多种致病性正痘病毒中，但不存在于牛痘病毒中，并且这些病毒蛋白中的任一种的表达阻断人细胞中的NF-κ B信号传导。因此，天花病毒的蛋白质组学筛选有可能揭示人类先天性抗病毒反应的调节剂。
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-kappa B1)/p105. This represents the first direct interaction between a pathogen-encoded protein and NF-kappa B1/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-kappa B signaling in human cells. Thus, proteomic screening of variola virus has the potential to uncover modulators of the human innate antiviral responses.