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

地方性牛白血病(EBL)是由牛白血病病毒(BLV)引起的。由于东北地区EBL发病频繁，BLV感染率很高，经济损失严重。另一方面，BLV和人类T细胞白血病病毒已被证明是逆转录病毒家族中一个独特的亚群，它可以诱发人类成人T细胞白血病。这一亚群具有独特的遗传内容、基因组结构和包括PX基因在内的基因表达策略，因此EBL作为理解人类恶性疾病的良好模型被寄予更多的期望。然而，BLV感染致癌的机制以及淋巴器官的致病机制仍有许多不清楚的地方。少数感染BLV的牛在很长一段潜伏期后会患上白血病。许多受感染的动物的抗BLV抗体血清学检测呈阳性，但它们仍处于健康的亚临床携带者状态。在感染的动物中，30%到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BoCD5阳性的B-1a细胞中显著增加，病毒基因的表达增加。只有不到1%的受感染动物会患上白血病和淋巴瘤，导致死亡。在长达4年的研究中发现：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BLV诱导的淋巴瘤的抵抗力和敏感性密切相关；3)携带BLV抗性MHC等位基因的绵羊对病毒有强烈的体液和细胞免疫应答；4)感染BLV的绵羊抑制淋巴细胞的凋亡，从而促进淋巴细胞的增殖；5)用PL或EBL增强牛的肿瘤坏死因子受体2型的表达。因此，与EBL的发展和抑制相关的一些因素变得清晰起来。

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.