权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Search of developmental and inhibitory factors in pathogenesis of enzootic bovine leukosis

牛地方性白血病发病机制中发育及抑制因素的探索

基本信息

批准号：
13460138
负责人：
OKADA Kosuke
金额：
$ 9.98万
依托单位：
Iwate University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

项目摘要

Enzootic bovine leukosis (EBL) is caused by bovine leukemia virus (BLV). Because EBL occurs frequently and the BLV-infection rate is very high, the economic damage is serious in the Tohoku area. On the other hand, it has been demonstrated that BLV and human T-cell leukemia virus, which induces human adult T-cell leukemia, constitute a unique subgroup within the retrovirus family. This subgroup is characterized by distinct genetic content, genomic organization, and strategy for gene expression including the pX gene, so more expectation is placed on EBL as a good model for understanding human malignant diseases. However, there are many unclear points, such as the mechanism of oncogenesis due to BLV infection and pathogenesis in lymphoid organs. A few BLV-infected cattle develop leukemia after a long latency period. Many of the infected animals become serologically positive for the anti-BLV antibody, but they remain in a healthy, subclinical carrier state. Of the infected animals, 30 to 35% develop persistent lymphocytosis (PL). In these animals, BLV provirus dramatically increases in BoCD5-positive B-1a cells, and expression of the viral gene increases. Less than 1% of infected animals develop leukemia and lymphoma resulting in death. During the present study, which spans a 4-year period, it became clear that 1)the difference in the activity types of viral tax gene does not effect the pathogenicity in sheep, 2)the major histocompatibility antigen (MHC) haplotypes are closely related to the resistance and sensitivity to BLV-induced lymphoma, 3)humeral and cellular immune responses are strongly induced against viruses in sheep with BLV-resistant MHC allele, 4)the inhibition of lymphocytic apotosis occurs in BLV-infected sheep, so proliferation of lymphocytes will be promoted, and 5)expression of tumor necrosis factor receptors type 2 increase in cattle with PL or EBL. Thus, a number of the factors associated with the development and inhibition of EBL became clear.

地方性牛白血病（EBL）是由牛白血病病毒（BLV）引起的。由于EBL发生频繁，BLV感染率很高，东北地区的经济损失严重。另一方面，已经证明BLV和诱导人成人T细胞白血病的人T细胞白血病病毒构成逆转录病毒家族中的独特亚组。该亚组的特征在于独特的遗传内容、基因组组织和包括pX基因在内的基因表达策略，因此更多的期望放在EBL上作为理解人类恶性疾病的良好模型。然而，目前对BLV感染致肿瘤的机制及淋巴器官的发病机制仍有许多不清楚的地方。一些BLV感染的牛在长潜伏期后发生白血病。许多受感染的动物成为血清学阳性的抗BLV抗体，但他们仍然处于健康的亚临床携带者状态。在受感染的动物中，30%至35%发展为持续性淋巴细胞增多症（PL）。在这些动物中，BLV前病毒在BoCD 5阳性B-1a细胞中显著增加，并且病毒基因的表达增加。不到1%的受感染动物发展为白血病和淋巴瘤，导致死亡。本研究历时4年，结果表明：1）病毒tax基因活性类型的差异不影响绵羊的致病性; 2）主要组织相容性抗原（MHC）单倍型与绵羊对BLV诱发淋巴瘤的抗性和敏感性密切相关; 3）具有BLV抗性MHC等位基因的绵羊对病毒产生强烈的体液免疫和细胞免疫应答，（4）BLV感染绵羊的淋巴细胞凋亡受到抑制，从而促进淋巴细胞的增殖;（5）PL或EBL牛的肿瘤坏死因子受体2型表达增加。因此，与EBL的发展和抑制相关的许多因素变得清晰。