INTERACTIONS OF BLV GP30 WITH B CELL SIGNAL PATHWAYS

已知许多淋巴组织增生性疾病是由病毒引起的。 感染，包括人T淋巴细胞病毒（HTLV）感染， 爱泼斯坦巴尔病毒。 牛白血病病毒（BLV）是一种逆转录病毒， 导致感染牛的非肿瘤性B淋巴细胞增殖 可能进展为淋巴瘤或白血病，与HTLV密切相关 无论是遗传学上还是淋巴细胞增殖的启动。 的 增殖机制尚未确定，但假设 正常增殖细胞的病毒蛋白干扰 在宿主细胞中的路径。 本项目的目标是检查 BLV跨膜蛋白gp 30在宿主细胞活化中的作用。 BLV跨膜蛋白gp 30与BLV的跨膜蛋白gp 30具有序列同源性。 B细胞和T细胞的正常信号转导。 在体外研究中， GP 30的嵌合体从细胞表面转导活化信号， 并且gp 30蛋白的突变已经显示出减少病毒感染 感染性和体内增殖。 拟议的研究将 试图确定gp 30在信号传递和B细胞中的作用 activation. 假设BLV跨膜蛋白gp 30 在感染的宿主淋巴细胞中启动酪氨酸激酶信号通路， 导致宿主细胞活化增加。 三个具体目标将是 用于检验假设：i）鉴定特定的酪氨酸激酶 与细胞质gp 30相互作用，ii）确定是否 gp 30表达的增加与 与gp 30相关的特定酪氨酸激酶的状态和iii） 确定所鉴定的酪氨酸激酶是否激活受感染的 淋巴细胞 这项研究应该提供深入了解的机制， B细胞中正常信号通路的研究以及病毒 可能会在感染过程中破坏这些机制。 候选人是 兽医完成比较病理学住院医师， 开始攻读比较病毒学/免疫学的博士学位 这位候选人有 完成了博士学位的教学阶段包括编写一份 独立研究计划。 该项目将使她 博士研究，并将提供方向的长期目标， 研究病毒/宿主相互作用和细胞调节的机制。 华盛顿州立大学和兽医系 微生物学和病理学有着悠久的成功培训历史， 研究生。 学院包括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.