NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
Front Cell Infect Microbiol. 2021 Dec 9;11:777955. doi: 10.3389/fcimb.2021.777955. eCollection 2021.
The development of malaria vaccines and medicines depends on the discovery of novel malaria protein targets, but the functions of more than 40% of genes remain unknown. Asexual parasites are the critical stage that leads to serious clinical symptoms and that can be modulated by malaria treatments and vaccines. To identify critical genes involved in the development of parasites within erythrocytes, the expression profile of more than 5,000 genes distributed across the 14 chromosomes of the PF3D7 strain during its six critical developmental stages (merozoite, early-ring, late-ring, early trophozoite, late-trophozoite, and middle-schizont) was evaluated. Hence, a qRT-PCR-based transcriptome of the erythrocytic developmental process of was revealed. Weighted gene coexpression network analyses revealed that a large number of genes are upregulated during the merozoite release process. Further gene ontology analysis revealed that a cluster of genes is associated with merozoite and may be apical complex components. Among these genes, 135 were comprised within chromosome 14, and 80% of them were previously unknown in functions. Western blot and immunofluorescence assays using newly developed corresponding antibodies showed that some of these newly discovered proteins are highly expressed in merozoites. Further invasion inhibition assays revealed that specific antibodies against several novel merozoite proteins can interfere with parasite invasion. Taken together, our study provides a developmental transcriptome of the asexual parasites of and identifies a group of previously unknown merozoite proteins that may play important roles in the process of merozoite invasion.
疟疾疫苗和药物的开发依赖于新型疟原蛋白靶标的发现,但超过 40%的基因的功能仍然未知。无性寄生虫是导致严重临床症状的关键阶段,可被疟疾治疗和疫苗调节。为了鉴定与红细胞内寄生虫发育相关的关键基因,评估了 PF3D7 株的 14 条染色体上超过 5000 个基因在其六个关键发育阶段(裂殖子、早期环、晚期环、早期滋养体、晚期滋养体和中裂殖体)的表达谱。因此,揭示了疟原虫红细胞发育过程的 qRT-PCR 转录组。加权基因共表达网络分析显示,大量基因在裂殖子释放过程中上调。进一步的基因本体分析显示,一组基因与裂殖子相关,可能是顶端复合物的组成部分。在这些基因中,有 135 个位于 14 号染色体上,其中 80%的基因以前在功能上是未知的。使用新开发的相应抗体进行的 Western blot 和免疫荧光分析表明,这些新发现的蛋白质中的一些在裂殖子中高度表达。进一步的入侵抑制实验表明,针对几种新型裂殖子蛋白的特异性抗体可以干扰寄生虫的入侵。总之,我们的研究提供了疟原虫无性寄生虫的发育转录组,并鉴定了一组以前未知的裂殖子蛋白,它们可能在裂殖子入侵过程中发挥重要作用。