Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología-CSIC, Darwin 3, 28049 Madrid, Spain.
Virol J. 2010 Mar 15;7:59. doi: 10.1186/1743-422X-7-59.
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.
痘病毒通过病毒编码的抑制剂的作用逃避宿主的免疫系统，这些抑制剂阻断各种信号通路。病毒抑制剂的确切数量尚不清楚。几种具有 Bcl-2 样结构的痘苗病毒 A46 和 N1 家族成员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 还通过类似于细胞 Bcl-2 蛋白的作用保持抗凋亡作用。是否存在具有类似功能的相关家族是本研究的主要课题。
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，它们在 C 末端共享约 110-140 个氨基酸的共同结构域，跨越整个 N1 序列。二级结构和折叠识别预测表明，该结构域呈现出与痘苗病毒蛋白 N1、A52、B15 和 K7 的 Bcl-2 样结构兼容的全α-螺旋折叠。我们建议将这些蛋白家族合并为一个家族。我们描述了该家族的系统发育分布，并重建了其进化历史，这表明祖先病毒的基因获得广泛，其基因内容进一步稳定。
基于序列/结构相似性，我们提出其他具有未知功能的成员，如痘苗病毒 N2、C1、C6 和 C16/B22，可能通过与 TLR 信号通路在不同水平上拮抗，在抑制宿主免疫反应方面发挥与 A46、A52、B15 和 K7 类似的作用。
