INTERACTIONS OF BLV GP30 WITH B CELL SIGNAL PATHWAYS

已知许多淋巴增生性疾病是由病毒引起的。 感染，包括感染人类T淋巴细胞病毒(HTLV)和 爱泼斯坦-巴尔病毒。牛白血病病毒(BLV)是一种逆转录病毒 引起感染牛的非肿瘤性B淋巴细胞增殖 可能进展为淋巴瘤或白血病，并与HTLV密切相关 无论是在遗传上还是在启动淋巴细胞增殖方面。这个 扩散机制尚未确定，但仍是假设的 由正常增殖的病毒蛋白扰动所致 宿主细胞中的通路。这个项目的目标是研究 BLV跨膜蛋白GP30在宿主细胞激活中的作用。 BLV跨膜蛋白GP30与BLV B细胞和T细胞信号转导均正常。在体外研究中， GP30的嵌合体从细胞表面传递激活信号， 而GP30蛋白的突变已经被证明可以减少病毒 体内的传染性和增殖性。拟议的研究将 试图确定GP30在信号传递和B细胞中的作用 激活。假设BLV跨膜蛋白GP30 在受感染的宿主淋巴细胞中启动酪氨酸激酶信号通路， 导致宿主细胞的激活增加。三个具体目标将是 用来检验假设：i)识别特定的酪氨酸激酶 与细胞质GP30相互作用，ii)决定水平是否 GP30的表达与细胞的存在和激活增强相关 与GP30和III相关的特定酪氨酸激酶的状态) 确定已识别的酪氨酸激酶是否激活受感染 淋巴细胞。这项研究应该为深入了解这种机制提供帮助。 B细胞的正常信号通路以及病毒通过的方法 可能会在感染过程中颠覆这些机制。候选人是一位 完成比较病理学实习的兽医 开始攻读比较病毒学/免疫学博士学位。候选人有 完成了博士课程的教学阶段，包括准备 独立研究提案。提议的项目构成了她 博士研究并将为长期目标提供方向 研究病毒/宿主相互作用和细胞调控的机制。 华盛顿州立大学和兽医系 微生物学和病理学有很长的成功培训历史 研究生。教职员工中有许多成功的研究人员。 在传染病领域与学生密切互动 研究人员。

Many lymphoproliferative disorders are known to result from viral infection including infection by human T lymphotropic virus (HTLV) and Epstein Barr virus. Bovine leukemia virus (BLV) is a retrovirus which causes a nonneoplastic B lymphocyte proliferation in infected cattle that may progress to lymphoma or leukemia and is closely related to HTLV both genetically and in the initiation of lymphocyte proliferation. The mechanism of proliferation has not been determined but is hypothesized to result from viral protein perturbation of normal proliferative pathways in the host cell. The goal of this project is to examine the role of the BLV transmembrane protein, gp30, on host cell activation. The BLV transmembrane protein, gp30, has sequence homology with the normal signal transducers of both B and T cells. In in vitro studies, chimeras of gp30 transduces activation signals from the cell surface, and mutation of the gp30 protein has been shown to decrease viral infectivity and proliferation in vivo. The proposed research will attempt to identify the role of gp30 in signal transmission and B cell activation. The hypothesis is that the BLV transmembrane protein gp30 initiates a tyrosine kinase signal pathway in infected host lymphocytes, leading to increased host cell activation. Three specific aims will be used to test the hypothesis: i) identifying specific tyrosine kinases that interact with cytoplasmic gp30, ii) determine whether the levels of gp30 expression correlate to the presence and increased activation status of specific tyrosine kinases associated with gp30 and iii) determining if the identified tyrosine kinases activate infected lymphocytes. This research should provide insight into the mechanisms of normal signal pathways in B cells as well as methods by which viruses may subvert these mechanisms during infection. The candidate is a veterinarian completing a comparative pathology residency and is starting a Ph.D in comparative virology/immunology. The candidate has completed the didactic phase of the Ph.D. including preparation of an independent research proposal. The proposed project constitutes her doctoral research and will provide direction for the long-term goal of investigating mechanisms of viral/host interactions and cell regulation. Washington State University and the Department of Veterinary Microbiology and Pathology have a long history of successfully training graduate students. The faculty includes numerous successful researchers in the field of infectious diseases and students closely interact with the researchers.