A poxvirus Bcl-2-like gene family involved in regulation of host immune response: sequence similarity and evolutionary history.
A poxvirus Bcl-2-like gene family involved in regulation of host immune response: sequence similarity and evolutionary history.
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DOI：
10.1186/1743-422x-7-59
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发表时间：
2010-03-15
期刊：
影响因子：
4.8
通讯作者：
Esteban M
中科院分区：
文献类型：
--
作者：
González JM;Esteban M
痘病毒通过阻断各种信号传导途径的病毒编码抑制剂的作用逃避宿主的免疫系统。病毒抑制剂的确切数量尚不清楚。牛痘病毒A46和N1家族的几个成员具有Bcl-2样结构，参与宿主先天免疫反应的调节，它们在Toll样受体信号通路的不同水平上非冗余地发挥作用。N1还通过与细胞Bcl-2蛋白类似的作用维持抗凋亡作用。是否有相关的家庭，可能有类似的功能是这次调查的主要主题。我们描述了痘病毒A46，N1，N2和C1蛋白家族之间存在的序列相似性，这些蛋白家族在其C-末端共享跨越整个N1序列的约110-140个氨基酸的共同结构域。二级结构和折叠识别预测表明，该结构域呈现与牛痘病毒蛋白N1、A52、B15和K7的Bcl-2样结构相容的全α螺旋折叠。我们建议，这些蛋白质家族应合并成一个单一的。我们描述了这个家族的系统发育分布，并重建了它的进化历史，这表明在祖先病毒中广泛的基因增益和其基因内容的进一步稳定。基于序列/结构的相似性，我们推测其他功能未知的成员，如牛痘病毒N2、C1、C6和C16/B22，可能与A46、A52、B15和K7在抑制宿主免疫应答中具有相似的作用，通过在不同水平上拮抗TLR信号通路。
Poxviruses evade the immune system of the host through the action of viral encoded inhibitors that block various signalling pathways. The exact number of viral inhibitors is not yet known. Several members of the vaccinia virus A46 and N1 families, with a Bcl-2-like structure, are involved in the regulation of the host innate immune response where they act non-redundantly at different levels of the Toll-like receptor signalling pathway. N1 also maintains an anti-apoptotic effect by acting similarly to cellular Bcl-2 proteins. Whether there are related families that could have similar functions is the main subject of this investigation. We describe the sequence similarity existing among poxvirus A46, N1, N2 and C1 protein families, which share a common domain of approximately 110-140 amino acids at their C-termini that spans the entire N1 sequence. Secondary structure and fold recognition predictions suggest that this domain presents an all-alpha-helical fold compatible with the Bcl-2-like structures of vaccinia virus proteins N1, A52, B15 and K7. We propose that these protein families should be merged into a single one. We describe the phylogenetic distribution of this family and reconstruct its evolutionary history, which indicates an extensive gene gain in ancestral viruses and a further stabilization of its gene content. Based on the sequence/structure similarity, we propose that other members with unknown function, like vaccinia virus N2, C1, C6 and C16/B22, might have a similar role in the suppression of host immune response as A46, A52, B15 and K7, by antagonizing at different levels with the TLR signalling pathways.