Florini Francesca, Visone Joseph E, Hadjimichael Evi, Malpotra Shivali, Nötzel Christopher, Kafsack Björn F C, Deitsch Kirk W
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA.
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.
Nat Microbiol. 2025 May 16. doi: 10.1038/s41564-025-02008-5.
Plasmodium falciparum evades antibody recognition through transcriptional switching between members of the var gene family, which encodes the major virulence factor and surface antigen on infected red blood cells. Previous work with clonal P. falciparum populations revealed var gene expression profiles inconsistent with uniform single var gene expression. However, the mechanisms underpinning this and how it might contribute to chronic infections were unclear. Here, using single-cell transcriptomics employing enrichment probes and a portable microwell system, we analysed var gene expression in clonal 3D7 and IT4 parasite lines. We show that in addition to mono-allelic var gene expression, individual parasites can simultaneously express multiple var genes or enter a state in which little or no var gene expression is detectable. Reduced var gene expression resulted in greatly decreased antibody recognition of infected cells. This transcriptional flexibility provides parasites with greater adaptive capacity and could explain the antigenically 'invisible' parasites observed in chronic asymptomatic infections.
恶性疟原虫通过var基因家族成员之间的转录转换来逃避抗体识别，该基因家族编码主要毒力因子和感染红细胞表面抗原。先前对克隆性恶性疟原虫群体的研究表明，var基因表达谱与单一var基因的均匀表达不一致。然而，其背后的机制以及它如何导致慢性感染尚不清楚。在这里，我们使用采用富集探针的单细胞转录组学和便携式微孔系统，分析了克隆的3D7和IT4寄生虫株系中的var基因表达。我们发现，除了单等位基因var基因表达外，单个寄生虫还可以同时表达多个var基因，或者进入几乎检测不到var基因表达的状态。var基因表达的降低导致感染细胞的抗体识别能力大大下降。这种转录灵活性为寄生虫提供了更大的适应能力，并可以解释在慢性无症状感染中观察到的抗原性“隐形”寄生虫。
