Department of Parasitology, Zhongshan School of Medicine, SunYat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People's Republic of China.
Parasitol Res. 2010 Sep;107(4):955-66. doi: 10.1007/s00436-010-1960-5. Epub 2010 Jul 3.
Schistosomes are the causative agent of schistosomiasis. The 70-kDa heat-shock proteins (HSP70) are considered the predominant HSP family and play a key regulatory role in parasite development and pathogenesis. Based on the published sequences in Genbank/EMBL, an open-reading frame (ORF) encoding 653 amino acids (XP_002581385.1) and belonging to the Schistosoma HSP70 protein family with a molecular weight of 71.49 kDa was identified by bioinformatic analysis. Since the sequence shared 77% identity with the published full-length Homo sapiens HSP70 protein, it was named Schistosoma mortalin-like protein (MLP/Hsp70). Here, we report the molecular and functional characterization of the Schistosoma japonicum SjMLP/hsp70 as a member of the HSP70 family. The complete SjMLP/hsp70 coding sequence was amplified from a S. japonicum adult worm cDNA library by polymerase chain reaction (PCR) and subcloned into the pET28a expression vector. The purified recombinant protein, rSjMLP/hsp70, was identified as a member of 70-kDa HSP family by mass spectrometry and could be recognized by the S. japonicum-infected mouse serum. Reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting analysis revealed that SjMLP/hsp70 was widely expressed in the eggs, cercariae, schistosomula, and adult worms of S. japonicum. A thermotolerance assay showed that rSjMLP/hsp70 could protect Escherichia coli cells from heat damage. This chaperone-like activity was demonstrated by full-length SjMLP/hsp70. The detection of specific antibody levels by indirect enzyme-linked immunosorbent assay and IFN-gamma secretion of splenocytes by ELISpot assay suggested that mice immunized with SjMLP/hsp70 were able to elicit Th1-type bias immune response. The challenge-protective experiment showed that DNA vaccine of SjGST combined with SjMLP/hsp70 could induce a 31.31% reduction of worm burden and 58.59% reduction of egg burden in intestinal tissue of immunized mice. Our results imply that SjMLP/hsp70 has a potential adjuvant function and might be a vaccine candidate for schistosomiaisis, which is the first report of the expression and preliminary characterization analysis of this molecule.
血吸虫是血吸虫病的病原体。70kDa 热休克蛋白(HSP70)被认为是主要的 HSP 家族,在寄生虫的发育和发病机制中发挥关键的调节作用。基于 Genbank/EMBL 中已发表的序列,通过生物信息学分析鉴定了一个编码 653 个氨基酸(XP_002581385.1)的开放阅读框(ORF),属于分子量为 71.49kDa 的血吸虫 HSP70 蛋白家族,与已发表的全长 Homo sapiens HSP70 蛋白具有 77%的同一性,因此被命名为血吸虫 mortalin 样蛋白(MLP/Hsp70)。在这里,我们报道了日本血吸虫 SjMLP/hsp70 作为 HSP70 家族成员的分子和功能特征。通过聚合酶链反应(PCR)从日本血吸虫成虫 cDNA 文库中扩增 SjMLP/hsp70 的完整编码序列,并亚克隆到 pET28a 表达载体中。通过质谱鉴定,纯化的重组蛋白 rSjMLP/hsp70 被鉴定为 70kDa HSP 家族的成员,并可被日本血吸虫感染的小鼠血清识别。逆转录聚合酶链反应(RT-PCR)和 Western blot 分析显示, SjMLP/hsp70 在日本血吸虫的卵、尾蚴、童虫和成虫中广泛表达。热耐受试验表明,rSjMLP/hsp70 可以保护大肠杆菌细胞免受热损伤。全长 SjMLP/hsp70 显示了这种伴侣样活性。间接酶联免疫吸附试验检测特异性抗体水平和 ELISpot 试验检测脾细胞 IFN-γ分泌表明,用 SjMLP/hsp70 免疫的小鼠能够诱导 Th1 型偏向免疫反应。攻毒保护实验表明,SjGST 的 DNA 疫苗与 SjMLP/hsp70 联合可使免疫小鼠的肠道组织中蠕虫负荷减少 31.31%,卵负荷减少 58.59%。我们的结果表明, SjMLP/hsp70 具有潜在的佐剂功能,可能是血吸虫病的候选疫苗,这是该分子表达和初步特征分析的首次报道。