变体之间的竞争是可以预测的,并有助于非洲试体的抗原变异动态
Douglas O Escrivani1, Viktor Scheidt1, Michele Tinti1
1Wellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dow Street, Dundee, United Kingdom.
PLoS pathogens
|July 17, 2023
概括
非洲试种体使用变异的表面糖蛋白 (VSGs) 进行免疫逃避. 激活微染色体VSG的细胞获得竞争优势,影响病原体动态.
科学领域:
- 寄生虫学的寄生虫学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 持久性病原体,如非洲试体,通过抗原变异逃避宿主免疫力.
- 变异性表面糖蛋白 (VSGs) 通过切换寄生虫的表面外来实现免疫逃避.
- 虽然VSG的切换顺序已知,但切换后的竞争动态尚不清楚.
研究的目的:
- 在VSG切换后,研究非洲试管体变体之间的竞争动态.
- 为了确定VSG竞争是否影响VSG表达的等级.
- 了解VSG类型对竞争优势的影响.
主要方法:
- 在实验室中,CRISPR-Cas9被用于诱导VSG基因重组和切换.
- RNA测序 (RNA-seq) 评估了独立于宿主免疫选择的VSG动态.
- 分析了切换三基因组克隆的差异生长和基因表达.
主要成果:
- 从压抑的表达部位激活VSG的三生体更频繁地发生.
- 激活小染色体VSGs的细胞表现出竞争优势,主导了人群.
- 这种优势在较长的VSGs中更为明显,并且与代谢和转化基因表达有关.
结论:
- 抗原变体,特别是非洲试体,在切换后积极竞争.
- 微染色体衍生VSG赋予了竞争优势,影响了人口动态.
- 变体之间的竞争会影响抗原变异,并延长免疫逃避.
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