Antigen variability in Anaplasma phagocytophilum during chronic infection of a reservoir host.
Antigen variability in Anaplasma phagocytophilum during chronic infection of a reservoir host.
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储存宿主慢性感染过程中嗜吞噬细胞无形体的抗原变异。
DOI：
10.1099/mic.0.059808-0
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Foley,Janet
中科院分区：
文献类型：
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作者：
Rejmanek,Daniel;Foley,Patrick;Barbet,Anthony;Foley,Janet
嗜吞噬细胞无形体是人类和其他动物的一种专性细胞内、蜱传播的细菌病原体。在感染过程中为了逃避宿主免疫，A. phagocytophilum利用基因转换将大约100个功能性假基因重组到themsp2(p44)基因的单个表达盒中，该基因编码主要表面抗原、主要表面蛋白2(Msp2)。 msp2(p44)重组在A的储存宿主中的作用和程度。吞噬细胞尚未被评估。在当前的研究中，我们探索了三只慢性感染林鼠（美国西部该疾病的储存库）中themsp2（p44）基因的重组模式和表达位点变异。所有三只林鼠均出现持续感染至少 6 个月的情况；其中两人持续活跃感染至少8个月。总共，我们检测到了 60 个独特的 msp2(p44) 表达位点变体的出现，在这三个 A 中没有共同的表达位点重组时间模式。嗜吞噬细胞群。在感染过程中，感染强度（即病原体负载）和sp2（p44）表达位点检测到的假基因的遗传多样性都会出现周期性波动。对基因组假基因耗竭率的分析表明，A 可用的假基因库。理论上，嗜吞噬细胞群可能会在一年内耗尽。然而，变异假基因的明显出现表明病原体可能无限期地逃避宿主免疫。我们的研究结果表明A之间存在紧密的共同进化关系。嗜吞噬细胞和林鼠中的病原体永远逃避宿主免疫，但不会引起可检测到的疾病。
Anaplasma phagocytophilumis an obligately intracellular, tick-transmitted, bacterial pathogen of humans and other animals. In order to evade host immunity during the course of infection,A. phagocytophilumutilizes gene conversion to shuffle approximately 100 functional pseudogenes into a single expression cassette of themsp2(p44)gene, which encodes the major surface antigen, major surface protein 2 (Msp2). The role and extent ofmsp2(p44)recombination in a reservoir host forA. phagocytophilumhave not been evaluated. In the current study, we explored patterns of recombination and expression site variability of themsp2(p44)gene in three chronically infected woodrats, a reservoir for the disease in the Western USA. All three woodrats developed persistent infection of at least 6 months duration; two of them maintained active infection for at least 8 months. In total, we detected the emergence of 60 uniquemsp2(p44)expression site variants with no common temporal patterns of expression site recombination among the threeA. phagocytophilumpopulations. Both the strength of infection (i.e. pathogen load) and the genetic diversity of pseudogenes detected at themsp2(p44)expression site fluctuated periodically during the course of infection. An analysis of the genomic pseudogene exhaustion rate showed that the repertoire of pseudogenes available to theA. phagocytophilumpopulation could in theory become depleted within a year. However, the apparent emergence of variant pseudogenes suggests that the pathogen could potentially evade host immunity indefinitely. Our findings suggest a tightly co-evolved relationship betweenA. phagocytophilumand woodrats in which the pathogen perpetually evades host immunity yet causes no detectable disease.