Wiebe Matthew S, Traktman Paula
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Cell Host Microbe. 2007 May 17;1(3):187-97. doi: 10.1016/j.chom.2007.03.007.
Barrier to autointegration factor (BAF) is a DNA-binding protein found in the nucleus and cytoplasm of eukaryotic cells that functions to establish nuclear architecture during mitosis. Herein, we demonstrate a cytoplasmic role for BAF in host defense during poxviral infections. Vaccinia is the prototypic poxvirus, a family of DNA viruses that replicate exclusively in the cytoplasm of infected cells. Mutations in the vaccinia B1 kinase (B1) compromise viral DNA replication, but the mechanism by which B1 achieves this has remained elusive. We now show that BAF acts as a potent inhibitor of poxvirus replication unless its DNA-binding activity is blocked by B1-mediated phosphorylation. These data position BAF as the effector of an innate immune response that prevents replication of exogenous viral DNA in the cytoplasm. To enable the virus to evade this defense, the poxviral B1 has evolved to usurp a signaling pathway employed by the host cell.
自身整合因子屏障（BAF）是一种在真核细胞的细胞核和细胞质中发现的DNA结合蛋白，其功能是在有丝分裂期间建立核结构。在此，我们证明了BAF在痘病毒感染期间宿主防御中的细胞质作用。痘苗病毒是痘病毒的原型，这是一类DNA病毒，仅在受感染细胞的细胞质中复制。痘苗病毒B1激酶（B1）的突变会损害病毒DNA复制，但其实现这一过程的机制仍不清楚。我们现在表明，除非其DNA结合活性被B1介导的磷酸化阻断，否则BAF可作为痘病毒复制的有效抑制剂。这些数据将BAF定位为一种先天性免疫反应的效应器，可防止外源性病毒DNA在细胞质中复制。为了使病毒能够逃避这种防御，痘病毒B1已经进化到篡夺宿主细胞使用的信号通路。
