Lo Chieh-Wen, Takeshima Shin-Nosuke, Okada Kosuke, Saitou Etsuko, Fujita Tatsuo, Matsumoto Yasunobu, Wada Satoshi, Inoko Hidetoshi, Aida Yoko
Laboratory of Global Animal Resource Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Laboratory of Global Infectious Diseases Control Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Pathogens. 2021 Apr 6;10(4):437. doi: 10.3390/pathogens10040437.
Bovine leukemia virus (BLV) causes enzootic bovine leucosis, a malignant B-cell lymphoma in cattle. The DNA sequence polymorphisms of bovine leukocyte antigen (BoLA) have exhibited a correlation with BLV-induced lymphoma in Holstein cows. However, the association may vary between different cattle breeds. Furthermore, little is known about the relationship between BLV-induced lymphoma and DRB3 at the amino acid and structural diversity levels. Here, we comprehensively analyzed the correlation between BLV-induced lymphoma and DRB3 at DNA, amino acid, and binding pocket property levels, using 106 BLV-infected asymptomatic and 227 BLV-induced lymphoma Japanese black cattle samples. was identified as a resistance allele, whereas and were susceptibility alleles. Amino acid association studies showed that positions 9, 11, 13, 26, 30, 47, 57, 70, 71, 74, 78, and 86 were associated with lymphoma susceptibility. Structure and electrostatic charge modeling further indicated that binding pocket 9 of resistance DRB3 was positively charged. In contrast, alleles susceptible to lymphoma were neutrally charged. Altogether, this is the first association study of polymorphisms with BLV-induced lymphoma in Japanese black cattle. In addition, our results further contribute to understanding the mechanisms regarding how polymorphisms mediate susceptibility to BLV-induced lymphoma.
牛白血病病毒（BLV）可引发地方流行性牛白血病，这是一种牛的恶性B细胞淋巴瘤。牛白细胞抗原（BoLA）的DNA序列多态性已显示出与荷斯坦奶牛中BLV诱导的淋巴瘤存在相关性。然而，这种关联在不同牛品种之间可能有所不同。此外，关于BLV诱导的淋巴瘤与DRB3在氨基酸和结构多样性水平之间的关系，人们了解甚少。在此，我们使用106份感染BLV的无症状日本黑牛样本和227份BLV诱导的淋巴瘤日本黑牛样本，全面分析了BLV诱导的淋巴瘤与DRB3在DNA、氨基酸和结合口袋特性水平上的相关性。 被鉴定为抗性等位基因，而 和 是易感等位基因。氨基酸关联研究表明，第9、11、13、26、30、47、57、70、71、74、78和86位氨基酸与淋巴瘤易感性相关。结构和静电荷建模进一步表明，抗性DRB3的结合口袋9带正电荷。相比之下，易患淋巴瘤的等位基因带中性电荷。总之，这是首次在日本黑牛中对 多态性与BLV诱导的淋巴瘤进行关联研究。此外，我们的结果进一步有助于理解 多态性如何介导对BLV诱导的淋巴瘤易感性的机制。
