Pathogen escape from host immunity by a genome program for antigenic variation
Pathogen escape from host immunity by a genome program for antigenic variation
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DOI：
10.1073/pnas.0605302103
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发表时间：
2006-11-28
影响因子：
11.1
通讯作者：
Frank, Steven A.
中科院分区：
文献类型：
--
作者：
Barbour, Alan G.;Dai, Qiyuan;Frank, Steven A.
媒介传播的赫氏疏螺旋体（Borrelia Hermsii）是一种回归热病原体，它可以在不同抗原变体之间切换表面蛋白的基因表达，从而在宿主体内引起连续的免疫逃逸波并增加传播的可能性。类似的抗原变异程序系统也存在于非洲锥虫和恶性疟原虫中。在这些示例中，各个变体的转换率在很大范围内有所不同。我们研究了赫氏芽胞杆菌如何确定两种实验感染中的转换率：一种是通过特定抗血清鉴定变体，另一种是根据 DNA 序列鉴定。变体抗原的未表达基因座复制到单个表达位点的速率由沉默基因座的外源特征决定，而不是由沉默位点的变体编码序列与单个表达位点之间的相似性决定。特别是有两个因素决定了转换率。一组元件与表达基因和沉默基因座的 5' 端重叠；元件之间更大的序列同一性与更高的转换率相关。第二组元件位于 3' 侧表达位点的侧翼，并出现在沉默位点下游不同距离处；元件距离沉默基因座越近，该基因座进入表达位点的转换率就越大。结合起来，基因组的这两个特征提供了一种简单的机制来调节转换率，由此沉默基因座形成表达位点的转换率层次结构。尽管切换层次结构会导致各个细胞发生随机变化，但宿主内变体的排序是半可预测的。
The vector-borne bacterium Borrelia hermsii, a relapsing fever agent, switches gene expression of a surface protein between different antigenic variants, thereby causing sequential waves of immune escape within hosts and increasing the likelihood of transmission. Analogous programmed systems of antigenic variation occur in African trypanosomes and Plasmodium falciparum. In these examples, switch rates to individual variants differ over a wide range. We studied how B. hermsii determines switch rates in two experimental infections: one where variants were identified by specific antisera and one based on identification by DNA sequence. Unexpressed loci of variant antigens copy into a single expression site at rates determined by extragenic features of silent loci rather than similarity between coding sequences of variants at silent sites and the single expression site. Two elements, in particular, determine switch rates. one set of elements overlaps the 5' ends of the expressed gene and the silent loci; greater sequence identity between elements was associated with a higher switch rate. The second set of elements flanks the expression site on the 3' side and occurs at variable distances downstream from silent loci; the nearer an element to a silent locus, the greater the switch rate of that locus into the expression site. In combination, these two features of the genome provide a simple mechanism to modulate switch rate whereby silent loci form a hierarchy of switch rates into the expression site. Although the switching hierarchy causes changes in individual cells that are stochastic, ordering of variants within hosts is semipredictable.