Characterization and gene expression analysis of the cir multi-gene family of Plasmodium chabaudi chabaudi (AS).

Characterization and gene expression analysis of the cir multi-gene family of Plasmodium chabaudi chabaudi (AS).
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DOI:
10.1186/1471-2164-13-125
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发表时间:
2012-03-29
期刊:
影响因子:
4.4
通讯作者:
Langhorne J
Langhorne J
中科院分区:
生物学2区
文献类型:
--
作者:
Lawton J;Brugat T;Yan YX;Reid AJ;Böhme U;Otto TD;Pain A;Jackson A;Berriman M;Cunningham D;Preiser P;Langhorne J

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pir基因是疟原虫中最大的多基因家族,其成员存在于间日疟原虫、诺氏疟原虫和啮齿类疟疾物种中。尽管pir基因占基因组的5%,但人们对pir基因编码的蛋白质的功能知之甚少。夏氏疟原虫在小鼠中引起慢性感染,这可能是由于抗原变异。在这个模型中,pir基因被称为cirs,可能参与了这一机制,从而逃避宿主的免疫反应。为了充分理解CIR蛋白在夏氏疟原虫感染期间的作用,需要对cir基因家族进行详细表征。对cir库进行注释,并对编码的CIR蛋白进行详细的生物信息学表征。鉴定了两个主要的亚家族,命名为A和B。每个亚家族的成员显示不同的氨基酸基序,因此预测已经经历了功能分歧。此外,通过RNA测序和微阵列分析整个cir库的表达。高达40%的cir基因库在寄生虫感染过程中表达,并可以确定占主导地位的cir转录本。此外,在夏氏疟原虫感染高峰期,观察到cir亚组之间的表达模式存在一些差异。最后,特异性cir基因在无性血液阶段的不同时间点表达。总之,大量的cir基因及其在整个红细胞内发育周期的表达表明,CIR蛋白可能是重要的寄生虫的生存。特别地,在夏氏疟原虫感染高峰时检测到显性cir转录物支持CIR蛋白表达的想法,并且可以在该寄生虫的生物学中执行重要功能。本文所述方法的进一步应用可允许阐明CIR亚家族A和B蛋白功能,包括它们对抗原变异和免疫逃避的贡献。
The pir genes comprise the largest multi-gene family in Plasmodium, with members found in P. vivax, P. knowlesi and the rodent malaria species. Despite comprising up to 5% of the genome, little is known about the functions of the proteins encoded by pir genes. P. chabaudi causes chronic infection in mice, which may be due to antigenic variation. In this model, pir genes are called cirs and may be involved in this mechanism, allowing evasion of host immune responses. In order to fully understand the role(s) of CIR proteins during P. chabaudi infection, a detailed characterization of the cir gene family was required. The cir repertoire was annotated and a detailed bioinformatic characterization of the encoded CIR proteins was performed. Two major sub-families were identified, which have been named A and B. Members of each sub-family displayed different amino acid motifs, and were thus predicted to have undergone functional divergence. In addition, the expression of the entire cir repertoire was analyzed via RNA sequencing and microarray. Up to 40% of the cir gene repertoire was expressed in the parasite population during infection, and dominant cir transcripts could be identified. In addition, some differences were observed in the pattern of expression between the cir subgroups at the peak of P. chabaudi infection. Finally, specific cir genes were expressed at different time points during asexual blood stages. In conclusion, the large number of cir genes and their expression throughout the intraerythrocytic cycle of development indicates that CIR proteins are likely to be important for parasite survival. In particular, the detection of dominant cir transcripts at the peak of P. chabaudi infection supports the idea that CIR proteins are expressed, and could perform important functions in the biology of this parasite. Further application of the methodologies described here may allow the elucidation of CIR sub-family A and B protein functions, including their contribution to antigenic variation and immune evasion.
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