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来自日本血吸虫单性感染和两性感染雌虫的差异表达蛋白的功能特征分析

Functional characterization of differentially expressed proteins coming from unisexual and bisexual infected Schistosoma japonicum female worms.

作者信息

Zhong Haoran, Qin Fanglin, Ren Yuqi, Li Xiaochun, Hou Ling, Gu Shaopeng, Jin Yamei

机构信息

National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China; Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China.

National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China; Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, PR China; College of Life Sciences, Shanghai Normal University, Shanghai, PR China.

出版信息

Exp Parasitol. 2023 May;248:108504. doi: 10.1016/j.exppara.2023.108504. Epub 2023 Mar 11.

Abstract

Schistosomiasis is an important zoonotic disease affecting up to 40 kinds of animals and is responsible for ∼250 million human cases per year. Due to the extensive use of praziquantel for the treatment of parasitic diseases, drug resistance has been reported. Consequently, novel drugs and effective vaccines are urgently needed for sustained control of schistosomiasis. Targeting reproductive development of Schistosoma japonicum could contribute to the control of schistosomiasis. In this study, five highly expressed proteins (S. japonicum large subunit ribosomal protein L7e, S. japonicum glutathione S-transferase class-mu 26 kDa isozyme, S. japonicum UDP-galactose-4-epimerase and two hypothetical proteins SjCAX70849 and SjCAX72486) in 18, 21, 23, and 25-day mature female worms compared to single-sex infected female worms were selected based on our previous proteomic analysis. Quantitative real-time polymerase chain reaction analysis and long-term interference with small interfering RNA were performed to identify the biological functions of these five proteins. The transcriptional profiles suggested that all five proteins participated in the maturation of S. japonicum. RNA interference against these proteins resulted in morphological changes to S. japonicum. The results of an immunoprotection assay revealed that immunization of mice with recombinant SjUL-30 and SjCAX72486 upregulated production of immunoglobulin G-specific antibodies. Collectively, the results demonstrated that these five differentially expressed proteins were vital to reproduction of S. japonicum and, thus, are potential candidate antigens for immune protection against schistosomiasis.

摘要

血吸虫病是一种重要的人畜共患病,可感染多达40种动物,每年导致约2.5亿人感染。由于广泛使用吡喹酮治疗寄生虫病,已报道出现耐药性。因此,迫切需要新型药物和有效的疫苗来持续控制血吸虫病。针对日本血吸虫的生殖发育进行研究有助于控制血吸虫病。在本研究中,根据我们之前的蛋白质组学分析,选择了18、21、23和25日龄成熟雌虫中与单性感染雌虫相比高表达的五种蛋白质(日本血吸虫大亚基核糖体蛋白L7e、日本血吸虫谷胱甘肽S-转移酶μ类26 kDa同工酶、日本血吸虫UDP-半乳糖-4-表异构酶以及两种假定蛋白SjCAX70849和SjCAX72486)。进行了定量实时聚合酶链反应分析和小干扰RNA长期干扰,以确定这五种蛋白质的生物学功能。转录谱表明,这五种蛋白质均参与了日本血吸虫的成熟过程。针对这些蛋白质的RNA干扰导致日本血吸虫形态发生变化。免疫保护试验结果显示,用重组SjUL-30和SjCAX72486免疫小鼠可上调免疫球蛋白G特异性抗体的产生。总体而言,结果表明这五种差异表达的蛋白质对日本血吸虫的繁殖至关重要,因此是抗血吸虫病免疫保护的潜在候选抗原。

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