A polymorphic multigene family encoding an immunodominant protein from Babesia microti.
A polymorphic multigene family encoding an immunodominant protein from Babesia microti.
复制标题
编码来自田鼠巴贝虫的免疫显性蛋白的多态性多基因家族。
DOI：
10.1128/jcm.38.1.362-368.2000
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发表时间：
2000
影响因子：
9.4
通讯作者：
Persing,DH
中科院分区：
文献类型：
--
作者：
Homer,MJ;Bruinsma,ES;Lodes,MJ;Moro,MH;Telford3rd,S;Krause,PJ;Reynolds,LD;Mohamath,R;Benson,DR;Houghton,RL;Reed,SG;Persing,DH
在美国，人类巴贝斯虫病主要由一种蜱传播的血液寄生虫-田鼠巴贝斯虫引起。需要改进检测该寄生虫感染的检测方法，因为无症状B。微生物感染是对血液供应的潜在威胁，小袋獾是地方性的我们对一个人分离的乙型肝炎病毒基因组DNA表达文库进行免疫筛选。microti（菌株MN 1）。在17个独特的免疫反应性克隆，我们确定了9个代表一个相关的基因家族与其他已知序列的同源性很小，但与结构类似的几个表面蛋白ofPlasmodium。在这个家族中，在N和C末端相对保守的片段之间发现了各种长度的简并六氨基酸重复序列（SEAGGP，SEAGWP，SGTGWP，SGTVGP）的串联阵列。为了检测克隆内变异，我们开发了一种PCR方法，直接从30个人血分离株、4个相应的仓鼠分离株和5个地理上相应的白足鼠分离株中回收特异性bmn 1 - 6同源物。从仓鼠中分离出的菌株与在相应的人类血液中发现的序列相同，这表明bmn 1 - 6的遗传变异在传代过程中不会发生。然而，来自不同患者的克隆在bmn 1 - 6同源物内简并重复序列的数量和位置方面往往彼此显著不同。此外，我们发现地理上密切相关的菌株在序列水平上也密切相关; 9名患者，均来自马萨诸塞州的南图克特岛，所含的克隆彼此难以区分，但与在其他东北部或上中西部菌株中发现的克隆不同。我们的结论是相当大的遗传和抗原多样性之间存在分离的B。来自美国的microtis和亚型的地理集群可能存在。bmn 1 - 6基因家族的性质表明了B的抗原变异机制。微滴可通过重组、差异表达或两种机制的组合而发生。
Human babesiosis in the United States is caused predominantly byBabesia microti, a tick-transmitted blood parasite. Improved testing methods for the detection of infection with this parasite are needed, since asymptomaticB. microtiinfection represents a potential threat to the blood supply in areas whereB. microtiis endemic. We performed immunoscreening of an expression library of genomic DNA from a human isolate ofB. microti(strain MN1). Among 17 unique immunoreactive clones, we identified 9 which represent a related family of genes with little sequence homology to other known sequences but with an architecture resembling that of several surface proteins ofPlasmodium. Within this family, a tandem array of a degenerate six-amino-acid repeat (SEAGGP, SEAGWP, SGTGWP, SGTVGP) was found in various lengths between relatively well conserved segments at the N and C termini. In order to examine within-clone variation, we developed a PCR protocol for direct recovery of a specificbmn1-6homologue directly from 30 human blood isolates, 4 corresponding hamster isolates, and 5 geographically correspondingPeromyscus leucopus(white-footed mouse) isolates. Isolates from the hamsters had the same sequences as those found in the corresponding human blood, suggesting that genetic variation ofbmn1-6does not occur during passage. However, clones from different patients were often substantially different from each other with regard to the number and location of the degenerate repeats within thebmn1-6homologue. Moreover, we found that strains that were closely related geographically were also closely related at the sequence level; nine patients, all from Nantucket Island, Mass., harbored clones that were indistinguishable from each other but that were distinct from those found in other northeastern or upper midwestern strains. We conclude that considerable genetic and antigenic diversity exists among isolates ofB. microtifrom the United States and that geographic clustering of subtypes may exist. The nature of thebmn1-6gene family suggests a mechanism of antigenic variation inB. microtithat may occur by recombination, differential expression, or a combination of both mechanisms.