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Merozoite Surface Antigen 2 Proteins of Babesia bovis Vaccine Breakthrough Isolates Contain a Unique Hypervariable Region Composed of Degenerate Repeats

机译:牛破壁杆菌疫苗突破分离株的裂殖子表面抗原2蛋白包含由简并重复组成的独特高变区

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The merozoite surface antigen 2 (MSA-2) proteins of Babesia bovis are members of the variable merozoite surface antigen (VMSA) family that have been implicated in erythrocyte invasion and are important targets for antibody-mediated blocking of invasion. Extensive sequence variation in another VMSA member, MSA-1, has been shown in all vaccine breakthrough isolates. To test the hypothesis that the msa-2 genes of vaccine breakthrough isolates would also encode a diverse set of proteins, the complete msa-2 locus was characterized from 12 Australian B. bovis strains and isolates, including two vaccine strains and eight vaccine breakthrough isolates, and compared to the loci in previously and newly characterized American strains. In contrast to American strains, the msa-2 loci of all Australian strains and isolates examined contain, in addition to msa-2c, only a solitary gene (designated msa-2a/b) closely related to American strain msa-2a and msa-2b. Nevertheless, the proteins encoded by these genes are quite diverse both between and within geographic regions and harbor evidence of genetic exchange among other VMSA family members, including msa-1. Moreover, all but one of the Australian breakthrough isolate MSA-2a/b proteins is markedly different from the vaccine strain from which immune escape occurred, consistent with their role in strain-specific protective immunity. The densest distribution of polymorphisms occurs in a hypervariable region (HVR) within the carboxy third of the molecule that is highly proline rich. Variation in length and content of the HVR is primarily attributable to differences in the order and number of degenerate nucleotide repeats encoding three motifs of unknown function.
机译:牛巴贝虫(Babesia bovis)的裂殖子表面抗原2(MSA-2)蛋白是可变裂殖子表面抗原(VMSA)家族的成员,与红细胞入侵有关,是抗体介导的阻断入侵。在所有疫苗突破分离株中均显示了另一个VMSA成员MSA-1的广泛序列变异。为了验证疫苗突破性分离株的 msa-2 基因也编码多种蛋白质的假设,从12个澳大利亚基因中鉴定出完整的 msa-2 基因座。 > B。牛病毒株和分离株,包括两个疫苗株和八个疫苗突破分离株,并与以前和新鉴定的美国株中的基因座进行了比较。与美国菌株相反,所有澳大利亚菌株和分离株的 msa-2 位点除 msa-2c 之外还仅包含一个孤独基因(称为 msa-2a / b )与美国菌株 msa-2a msa-2b 密切相关。但是,这些基因编码的蛋白质在地理区域之间和地理区域之内差异很大,并且具有VMSA其他家族成员,包括 msa-1 之间遗传交换的证据。此外,除一种澳大利亚突破性分离株MSA-2a / b蛋白外,其余所有蛋白均与发生免疫逃逸的疫苗株显着不同,与其在株特异性保护性免疫中的作用一致。多态性的最密集分布发生在高度脯氨酸丰富的分子羧基三分之一内的高变区(HVR)中。 HVR长度和含量的变化主要归因于编码未知功能的三个基序的简并核苷酸重复序列的顺序和数量的差异。

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