Zhai Qi, Huang Bing, Dong Hui, Zhao Qiping, Zhu Shunhai, Liang Siting, Li Sha, Yang Sihan, Han Hongyu
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Animal Parasitology of Ministry of Agriculture, Minhang, Shanghai, PR China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, PR China.
PLoS One. 2016 Jun 16;11(6):e0157678. doi: 10.1371/journal.pone.0157678. eCollection 2016.
The genome sequences of Eimeria tenella have been sequenced, but >70% of these genes are currently categorized as having an unknown function or annotated as conserved hypothetical proteins, and few of them have been studied. In the present study, a conserved hypothetical protein gene of E. tenella, designated EtCHP559, was cloned using rapid amplification of cDNA 5'-ends (5'RACE) based on the expressed sequence tag (EST). The 1746-bp full-length cDNA of EtCHP559 contained a 1224-bp open reading frame (ORF) that encoded a 407-amino acid polypeptide with the predicted molecular weight of 46.04 kDa. Real-time quantitative PCR analysis revealed that EtCHP559 was expressed at higher levels in sporozoites than in the other developmental stages (unsporulated oocysts, sporulated oocysts and second generation merozoites). The ORF was inserted into pCold-TF to produce recombinant EtCHP559. Using western blotting, the recombinant protein was successfully recognized by rabbit serum against E. tenella sporozoites. Immunolocalization by using EtCHP559 antibody showed that EtCHP559 was mainly distributed on the parasite surface in free sporozoites and became concentrated in the anterior region after sporozoites were incubated in complete medium. The EtCHP559 became uniformly dispersed in immature and mature schizonts. Inhibition of EtCHP559 function using anti-rEtCHP559 polyclonal antibody reduced the ability of E. tenella sporozoites to invade host cells by >70%. Animal challenge experiments demonstrated that the recombinant EtCHP559 significantly increased the average body weight gain, reduced the oocyst outputs, alleviated cecal lesions of the infected chickens, and resulted in anticoccidial index >160 against E. tenella. These results suggest that EtCHP559 plays an important role in sporozoite invasion and could be an effective candidate for the development of a new vaccine against E. tenella.
柔嫩艾美耳球虫的基因组序列已被测序,但其中超过70%的基因目前被归类为功能未知或注释为保守的假设蛋白,且对它们的研究很少。在本研究中,基于表达序列标签(EST),利用cDNA 5'-末端快速扩增(5'RACE)技术克隆了柔嫩艾美耳球虫一个保守的假设蛋白基因,命名为EtCHP559。EtCHP559的1746 bp全长cDNA包含一个1224 bp的开放阅读框(ORF),编码一个407个氨基酸的多肽,预测分子量为46.04 kDa。实时定量PCR分析显示,EtCHP559在子孢子中的表达水平高于其他发育阶段(未孢子化卵囊、孢子化卵囊和第二代裂殖子)。将该ORF插入pCold-TF中以产生重组EtCHP559。通过蛋白质免疫印迹法,重组蛋白成功被抗柔嫩艾美耳球虫子孢子的兔血清识别。使用EtCHP559抗体进行免疫定位显示,EtCHP559主要分布在游离子孢子的寄生虫表面,在子孢子在完全培养基中孵育后集中在前部区域。EtCHP559在未成熟和成熟裂殖体中均匀分散。使用抗rEtCHP559多克隆抗体抑制EtCHP559功能可使柔嫩艾美耳球虫子孢子侵入宿主细胞的能力降低70%以上。动物攻毒实验表明,重组EtCHP559显著增加了平均体重增加量,减少了卵囊产量,减轻了感染鸡的盲肠病变,并导致针对柔嫩艾美耳球虫的抗球虫指数>160。这些结果表明,EtCHP559在子孢子入侵中起重要作用,可能是开发针对柔嫩艾美耳球虫的新型疫苗的有效候选物。