Mapping of CD4+ T-cell epitopes in bovine leukemia virus from five cattle with differential susceptibilities to bovine leukemia virus disease progression
Mapping of CD4+ T-cell epitopes in bovine leukemia virus from five cattle with differential susceptibilities to bovine leukemia virus disease progression
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DOI：
10.1186/s12985-019-1259-9
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发表时间：
2019-12-16
期刊：
影响因子：
4.8
通讯作者：
Aida, Yoko
中科院分区：
文献类型：
--
作者：
Bai, Lanlan;Takeshima, Shin-nosuke;Aida, Yoko
背景牛白血病病毒（BLV）与人T细胞白血病病毒密切相关，是地方性牛白血病的病原体，这种疾病的特点是病程高度延长，涉及持续性淋巴细胞增多和B细胞淋巴瘤。牛主要组织相容性复合物 II 类区域在 BLV 感染的亚临床进展中发挥着关键作用。在本研究中，我们旨在评估 CD4(+) T 细胞表位在牛疾病进展中的作用。方法 我们检测了 5 头日本黑牛，包括 3 头易感动物、1 头抗病动物和 1 头正常动物，采用基于聚合酶链反应序列的分型方法，根据牛白细胞抗原 (BoLA)-DRB3 和 BoLA-DQA1 等位基因的基因分型进行分类。所有牛都接种了从实验性感染 BLV 的牛身上收集的 BLV 感染血液，然后通过细胞增殖测定进行 CD4(+) T 细胞表位作图。结果5头日本黑牛成功感染BLV，并进行CD4(+)T细胞表位作图。抗病牛和正常牛表现出低和中等的原病毒载量，并分别含有六种或五种类型的CD4(+) T细胞表位。相比之下，原病毒载量最高的三头疾病易感牛中的一头不含有CD4(+) T细胞表位，而原病毒载量较高的其他三头牛中的两头各只有一个表位。因此，CD4(+) T 细胞表位库在疾病易感牛中的频率低于其他牛。结论 虽然本研究只纳入了几头牛，但我们的结果表明 CD4(+) T 细胞表位可能与 BoLA-DRB3-DQA1 单倍型相关，这赋予了 BLV 前病毒载量不同的易感性。这些 CD4(+) T 细胞表位可用于设计针对疾病易感的日本黑牛的抗 BLV 疫苗。需要对其他品种的 CD4(+) T 细胞表位进行进一步研究，并使用大量具有不同敏感性的牛来证实这些发现。
Background Bovine leukemia virus (BLV), which is closely related to human T-cell leukemia virus, is the etiological agent of enzootic bovine leukosis, a disease characterized by a highly prolonged course involving persistent lymphocytosis and B-cell lymphoma. The bovine major histocompatibility complex class II region plays a key role in the subclinical progression of BLV infection. In this study, we aimed to evaluate the roles of CD4(+) T-cell epitopes in disease progression in cattle. Methods We examined five Japanese Black cattle, including three disease-susceptible animals, one disease-resistant animal, and one normal animal, classified according to genotyping of bovine leukocyte antigen (BoLA)-DRB3 and BoLA-DQA1 alleles using polymerase chain reaction sequence-based typing methods. All cattle were inoculated with BLV-infected blood collected from BLV experimentally infected cattle and then subjected to CD4(+) T-cell epitope mapping by cell proliferation assays. Results Five Japanese Black cattle were successfully infected with BLV, and CD4(+) T-cell epitope mapping was then conducted. Disease-resistant and normal cattle showed low and moderate proviral loads and harbored six or five types of CD4(+) T-cell epitopes, respectively. In contrast, the one of three disease-susceptible cattle with the highest proviral load did not harbor CD4(+) T-cell epitopes, and two of three other cattle with high proviral loads each had only one epitope. Thus, the CD4(+) T-cell epitope repertoire was less frequent in disease-susceptible cattle than in other cattle. Conclusion Although only a few cattle were included in this study, our results showed that CD4(+) T-cell epitopes may be associated with BoLA-DRB3-DQA1 haplotypes, which conferred differential susceptibilities to BLV proviral loads. These CD4(+) T-cell epitopes could be useful for the design of anti-BLV vaccines targeting disease-susceptible Japanese Black cattle. Further studies of CD4(+) T-cell epitopes in other breeds and using larger numbers of cattle with differential susceptibilities are required to confirm these findings.