Retrovirus Models of Lymphocyte Transformation/Disease

淋巴细胞转化/疾病的逆转录病毒模型

• 批准号: 7059991
• 负责人: MICHAEL D. LAIRMORE
• 金额: $ 198.03万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-21 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7059991
• 关键词: Retroviridae; cell transformation; clinical research; disease /disorder model; lymphocyte; model design /development; oncogenic virus; virus cytopathogenic effect; virus infection mechanism; virus replication

DESCRIPTION (provided by applicant): The study of regulatory and accessory proteins and virus encoded enzymes of complex retroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and human immunodeficiency virus (HIV) and have provided fundamental knowledge to define mechanisms of viral-induced transformation and basic paradigms of cell biology. This Program Project Grant (PPG) application is focused on using retrovirus models to elucidate basic cellular mechanisms governing transcriptional regulation of lymphocytes. This understanding will lead to new insights into the interface between pathogenic mechanisms of the virus during its replication and therapeutic modalities against retroviral-induced cancer. Each project will significantly expand ongoing collaborative efforts between the PPG laboratories. Project #1 is seeking to understand the essential role of p12I and p30II in transcriptional regulation in T-lymphocytes and in the establishment of HTLV-1 infection in vivo. Project #2 will extend the fundamental knowledge that defines the role of phosphorylation in HTLV Rex and thereby learn how this viral protein can be used to study mRNA transport in T-lymphocytes. Project #3 will test post-transcriptional control of retrovirus cell interaction through the use of novel control elements and retroviral vectors. Project #4 defines the role and regulation of parathyroid hormone related protein in ATL and its associated paraneoplastic syndrome, humoral hypercalcemia of malignancy in human and animal models. Project #5 continues the productive collaboration between The Ohio State University and Washington University, St. Louis to determine the role of the regulatory protein Tax in lymphocyte proliferation and virus-associated disease. Three interactive cores support the PPG: Administration/Biostatistics, Imaging, and Animal Models. The overall goal of the PPG is to use retrovirus models to define important mechanisms that determine lymphocyte proliferation and associated disease, as well as to test innovative modalities to ablate the effects of retroviral carcinogenesis.

描述（由申请人提供）：对人类 T 淋巴细胞病毒 1 型 (HTLV-1) 和人类免疫缺陷病毒 (HIV) 等复杂逆转录病毒的调节蛋白和辅助蛋白以及病毒编码酶的研究，并为定义机制提供了基础知识病毒诱导的转化和细胞生物学的基本范式。该计划项目拨款 (PPG) 申请的重点是使用逆转录病毒模型来阐明控制淋巴细胞转录调节的基本细胞机制。这种理解将使人们对病毒复制过程中的致病机制与逆转录病毒诱导的癌症的治疗方式之间的相互作用产生新的见解。每个项目都将显着扩大 PPG 实验室之间正在进行的合作。项目 #1 旨在了解 p12I 和 p30II 在 T 淋巴细胞转录调节和体内 HTLV-1 感染建立中的重要作用。项目 #2 将扩展定义 HTLV Rex 中磷酸化作用的基础知识，从而了解如何使用这种病毒蛋白来研究 T 淋巴细胞中的 mRNA 转运。项目 #3 将通过使用新型控制元件和逆转录病毒载体来测试逆转录病毒细胞相互作用的转录后控制。项目 #4 定义了甲状旁腺激素相关蛋白在 ATL 及其相关副肿瘤综合征、人类和动物模型中恶性肿瘤的体液高钙血症中的作用和调节。项目 #5 继续俄亥俄州立大学和圣路易斯华盛顿大学之间的富有成效的合作，以确定调节蛋白 Tax 在淋巴细胞增殖和病毒相关疾病中的作用。三个交互式核心支持 PPG：管理/生物统计学、成像和动物模型。 PPG 的总体目标是利用逆转录病毒模型来定义决定淋巴细胞增殖和相关疾病的重要机制，并测试消除逆转录病毒致癌作用的创新模式。