禽白血病病毒J亚群诱导免疫耐受发生的分子机制

Host immunotolerance induced by avian leukosis virus subgroup J (ALV-J) is prerequisite for subclinic symptom and neoplasm. It showed great harm to poultry Industry. However, little is known about the molecular mechanism of immunotolerance. Base on the previous study, we set up a vertical transmission model according to the behavior characteristics of ALV-J. The vertical transmission of ALV-J will induce different infection states including immunotolerance. First step, reservoir cells of ALV-J will be identified by cellular immunology technology, for elucidating how ALV-J hide itself, and next step the role of reservoir cells will be determined in immunotolerance processs. Further, we will detect how ALV-J blocks the antibody and cytokine produce, and how they interact in immune cells, for elucidating how ALV-J create outside condition for its replication to escape the immune system attack. Last, under the immunotolerance state, the sequence of ALV-J that lives in each tissue will be tested for the determination of quasispecies ecology and its evolutive discipline. Taken together, elucidating the molecular mechanism of immunotolerance induced by ALV-J would provide theory foundation for ALV-J control and immunotolerance research of other associated viruses.

禽白血病病毒J亚群（ALV-J）诱导宿主产生的免疫耐受是亚临床症状及肿瘤形成的必要条件，严重危害了家禽养殖业的发展。ALV-J诱导免疫耐受发生的分子机制仍未阐明。在前期研究的基础上，根据ALV-J感染行为特征，模拟垂直传播，建立ALV-J诱导的以免疫耐受为主的感染状态模型，利用生命科学前沿技术，通过细胞免疫学检测，明确ALV-J潜伏的贮主细胞及其对免疫耐受形成的影响；通过组学检测ALV-J感染的免疫细胞，研究ALV-J阻断免疫细胞抗体及细胞因子生成途径，明确ALV-J与抗体、细胞因子生成信号通路分子的互作，揭示ALV-J逃避免疫细胞攻击机制；通过动态检测不同感染状态下各组织器官ALV-J核酸序列，揭示ALV-J准种生态及其演变规律，明确ALV-J变异与免疫耐受的相关性。ALV-J诱导免疫耐受发生的分子机制解析，为ALV-J防控及相关病毒免疫耐受研究提供了科学基础。

基于ALV-J诱导的免疫耐受对养禽业的危害，阐明其免疫耐受的分子机制是当前的紧迫任务。本研究通过建立ALV-J诱导的免疫耐受模型，以现代生命科学前沿技术手段，从宿主和ALV-J两方面分别明确ALV-J潜伏的贮主细胞及其对免疫耐受形成的影响。通过检测ALV-J阻断免疫细胞抗体及细胞因子生成途径，ALV-J与抗体、细胞因子生成信号通路分子互作，成功鉴定了法氏囊中CD117+chB6+祖B细胞为ALV-J的贮主细胞，证明ALV-J诱导的免疫耐受是由于ALV-J阻断了其抗体分泌，而不是通常认为的诱导B细胞的凋亡引起的；lyn介导的BCR信号转导抑制是CD117+chB6+祖B细胞抗体分泌受阻的直接原因；ALV-J通过招募宿主细胞CTHRC1分子促进自身的快速复制，从而保证了诱导机体持续的免疫耐受；进一步明确了免疫耐受状态下ALV-J准种的演变规律。最终，阐明了ALV-J诱导免疫耐受的分子机制。