Retrovirus Models of Lymphocyte Transformation and Disease- Competing Supplement

淋巴细胞转化和疾病竞争补充剂的逆转录病毒模型

• 批准号: 7016237
• 负责人: MICHAEL D. LAIRMORE
• 金额: $ 4.95万
• 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/7016237
• 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) have provided fundamental knowledge to define mechanisms of viral-induced transformation and basic paradigms of cell biology. The Program Project Grant (PPG) application is focused on using retrovirus models to elucidate basic cellular mechanism 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 p12 and p30 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 humans and animals 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）：对复杂逆转录病毒（如人嗜T淋巴细胞病毒1型（HTLV-1）和人免疫缺陷病毒（HIV））的调节和辅助蛋白以及病毒编码酶的研究为定义病毒诱导转化的机制和细胞生物学的基本范式提供了基础知识。计划项目资助（PPG）的应用重点是使用逆转录病毒模型来阐明淋巴细胞转录调控的基本细胞机制。这一认识将导致新的见解之间的接口病毒的致病机制在其复制和治疗方式对逆转录病毒引起的癌症。每个项目都将大大扩展PPG实验室之间正在进行的合作。项目#1试图了解p12和p30在T淋巴细胞转录调控和体内HTLV-1感染建立中的重要作用。项目#2将扩展定义HTLV雷克斯中磷酸化作用的基础知识，从而了解这种病毒蛋白如何用于研究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定义了甲状旁腺相关蛋白在人类和动物模型中ATL及其相关副肿瘤综合征、恶性肿瘤体液性高钙血症中的作用和调节。项目#5继续俄亥俄州州立大学和华盛顿大学圣路易斯分校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的总体目标是使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，以及测试消除逆转录病毒致癌作用的创新模式。