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A role for Z-DNA binding in vaccinia virus pathogenesis

机译:Z-DNA结合在痘苗病毒发病机理中的作用

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摘要

The N-terminal domain of the E3L protein of vaccinia virus has sequence similarity to a family of Z-DNA binding proteins of defined three-dimensional structure and it is necessary for pathogenicity in mice. When other Z-DNA-binding domains are substituted for the similar E3L domain, the virus retains its lethality after intracranial inoculation. Mutations decreasing Z-DNA binding in the chimera correlate with decreases in viral pathogenicity, as do analogous mutations in wild-type E3L. A chimeric virus incorporating a related protein that does not bind Z-DNA is not pathogenic, but a mutation that creates Z-DNA binding makes a lethal virus. The ability to bind the Z conformation is thus essential to E31L activity. This finding may allow the design of a class of antiviral agents, including agents against variola (smallpox), which has an almost identical E3L. [References: 29]
机译:牛痘病毒E3L蛋白的N端结构域与定义的三维结构的Z-DNA结合蛋白家族具有序列相似性,并且对小鼠具有致病性。当其他Z-DNA结合结构域取代相似的E3L结构域时,病毒在颅内接种后仍保持其致死性。降低嵌合体中Z-DNA结合的突变与病毒致病性降低相关,野生型E3L中的类似突变也是如此。掺入不结合Z-DNA的相关蛋白质的嵌合病毒不是致病性的,但是产生Z-DNA结合的突变会导致致命的病毒。因此,结合Z构象的能力对于E31L活性是必不可少的。这一发现可能允许设计一类抗病毒药物,包括抗天花(天花)的药物,其具有几乎相同的E3L。 [参考:29]

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