| Co-Investigator(Kenkyū-buntansha) |
AIDA Yoko RIKEN, Retrovirus Research Unit, Unit leader, 分子ウイルス学研究ユニット, ユニットリーダー (82401999)
ONUMA Misao Hokkaido University, Graduate School of Veterinary Medicine, Professor, 大学院・獣医学研究科, 教授 (70109510)
GORYO Masanobu Iwate University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (80153774)
HIRATA Toh-ichi Iwate University, Faculty of Agriculture, Research Associate, 農学部, 助手 (20241490)
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| Research Abstract |
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.
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