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来自球形蛋白4:一个含有保守B细胞表位并在……中诱导交叉反应性中和抗体的新基因。

Spherical Body Protein 4 from : A Novel Gene That Contains Conserved B-Cell Epitopes and Induces Cross-Reactive Neutralizing Antibodies in .

作者信息

Mosqueda Juan, Hernandez-Silva Diego Josimar, Ueti Massaro W, Cruz-Reséndiz Adolfo, Marquez-Cervantez Ricardo, Valdez-Espinoza Uriel Mauricio, Dang-Trinh Minh-Anh, Nguyen Thu-Thuy, Camacho-Nuez Minerva, Mercado-Uriostegui Miguel Angel, Aguilar-Tipacamú Gabriela, Ramos-Aragon Juan Alberto, Hernandez-Ortiz Ruben, Kawazu Shin-Ichiro, Igarashi Ikuo

机构信息

Immunology and Vaccines Laboratory, C. A. Facultad de Ciencias Naturales, Universidad Autonoma de Queretaro, Carretera a Chichimequillas, Ejido Bolaños, Queretaro 76140, Mexico.

C.A. Salud Animal y Microbiologia Ambiental, Facultad de Ciencias Naturales, Universidad Autonoma de Queretaro, Av. de las Ciencias s/n Col Juriquilla, Queretaro 76230, Mexico.

出版信息

Pathogens. 2023 Mar 22;12(3):495. doi: 10.3390/pathogens12030495.

Abstract

Bovine babesiosis is a tick-transmitted disease caused by intraerythrocytic protozoan parasites of the genus . Its main causative agents in the Americas are and while affects cattle in Asia. All species secrete proteins stored in organelles of the apical complex, which are involved in all steps of the invasion process of vertebrate host cells. Unlike other apicomplexans, which have dense granules, babesia parasites instead have large, round intracellular organelles called spherical bodies. Evidence suggests that proteins from these organelles are released during the process of invading red blood cells, where spherical body proteins (SBPs) play an important role in cytoskeleton reorganization. In this study, we characterized the gene that encodes SBP4 in . This gene is transcribed and expressed in the erythrocytic stages of . The gene consists of 834 nucleotides without introns that encode a protein of 277 amino acids. In silico analysis predicted a signal peptide that is cleaved at residue 20, producing a 28.88-kDa protein. The presence of a signal peptide and the absence of transmembrane domains suggest that this protein is secreted. Importantly, when cattle were immunized with recombinant SBP4, antibodies identified and merozoites according to confocal microscopy observations and were able to neutralize parasite multiplication in vitro for both species. Four peptides with predicted B-cell epitopes were identified to be conserved in 17 different isolates from six countries. Compared with the pre-immunization sera, antibodies against these conserved peptides reduced parasite invasion in vitro by 57%, 44%, 42%, and 38% for peptides 1, 2, 3, and 4, respectively ( < 0.05). Moreover, sera from cattle infected with cattle contained antibodies that recognized the individual peptides. All these results support the concept of as a new gene in that should be considered a candidate for a vaccine to control bovine babesiosis.

摘要

牛巴贝斯虫病是一种由巴贝斯属红细胞内原生动物寄生虫引起的蜱传播疾病。在美洲,其主要病原体是双芽巴贝斯虫和分歧巴贝斯虫,而东方巴贝斯虫影响亚洲的牛。所有巴贝斯虫物种都会分泌储存在顶复合器细胞器中的蛋白质,这些蛋白质参与脊椎动物宿主细胞入侵过程的所有步骤。与其他具有致密颗粒的顶复门原虫不同,巴贝斯虫寄生虫具有称为球形体的大型圆形细胞内细胞器。有证据表明,这些细胞器中的蛋白质在侵入红细胞的过程中释放,其中球形体蛋白(SBPs)在细胞骨架重组中起重要作用。在本研究中,我们对编码双芽巴贝斯虫SBP4的基因进行了表征。该基因在双芽巴贝斯虫的红细胞阶段转录并表达。双芽巴贝斯虫基因由834个无内含子的核苷酸组成,编码一个277个氨基酸的蛋白质。计算机分析预测了一个在第20位残基处切割的信号肽,产生一个28.88 kDa的蛋白质。信号肽的存在和跨膜结构域的缺失表明该蛋白质是分泌型的。重要的是,当用重组双芽巴贝斯虫SBP4免疫牛时,根据共聚焦显微镜观察,抗体识别双芽巴贝斯虫和分歧巴贝斯虫裂殖子,并且能够在体外中和这两个物种的寄生虫增殖。在来自六个国家的17个不同分离株中鉴定出四个具有预测B细胞表位的肽是保守的。与免疫前血清相比,针对这些保守肽的抗体分别使肽1、2、3和4的体外寄生虫入侵减少了57%、44%、42%和38%(P < 0.05)。此外,感染双芽巴贝斯虫的牛的血清中含有识别单个肽的抗体。所有这些结果支持将双芽巴贝斯虫SBP4作为双芽巴贝斯虫中的一个新基因的概念,该基因应被视为控制牛巴贝斯虫病疫苗的候选基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f5a/10051436/b673bef197c2/pathogens-12-00495-g001.jpg

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