2018 Fiscal Year Final Research Report
Identification and functional analyses of host factors are associated with bovine leukemia virus proviral load by genome-wide association study and genome-wide transcriptional profiling
| Project/Area Number |
16H02590
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Veterinary medical science
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Aida Yoko 国立研究開発法人理化学研究所, 開拓研究本部, 研究員 (50182994)
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| Co-Investigator(Kenkyū-buntansha) |
水谷 哲也 東京農工大学, 農学部, 教授 (70281681)
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| Research Collaborator |
Takeshima Shin-nosuke
Sato Hirotaka
Otsuki Hiroyuki
Shimoji Yoshihiro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 牛白血病ウイルス / プロウイルス量 / ゲノムワイド相関解析 / プロテオミクス解析 / 体内ウイルス量制御因子 / SNPマーカー / MMR遺伝子 / RNA-seq解析 |
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| Outline of Final Research Achievements |
Using whole genome association study, we successfully identified three SNPs showing a significant association with BLV proviral load. Furthermore, we injected white blood cells derived from BLV-infected cow. Using RNA-seq analyss of RNA prepared from these cattle, we found MMR gene involved in BLV proviral load. Moreover, the expression of MMR gene increases in BLV-infected but healthy cattle, while it decreased in BLV-infected cattle with lymphoma, as determined by real-time quantitative reverse transcription-polymerase chain reaction. In addition, the expression of MMR gene increased in cells transiently and stably transfected with an infectious molecular clones of BLV. Our result shows that the expression of MMR gene was maintained at high level in early infection stage of BLV thereby stabilizing genome, while it decreased in tumor stage thereby increasing rates of spontaneous mutation in genome.
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| Free Research Field |
ウイルス感染症
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| Academic Significance and Societal Importance of the Research Achievements |
BLVプロウイルス量は、EBLの病態進行および発症のマーカーとなることが明らかになっている。従って、本研究により低・高プロウイルス量の特異的SNPマーカーとプロウイルス量を規定する新規宿主因子を同定できたことは、高プロウイルス量関連宿主因子保有個体から優先的に淘汰する戦略に、一方、低プロウイルス量関連宿主因子保有個体はウイルス量を増加させない、発症しにくいウシを作出するという育種戦略に有効であることから、BLVの清浄化に大きく貢献する成果として、者会的意義は大きいといえる。
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