Structure-Function Analyses of HIV Rev and HTLV Rex

描述（由申请人提供）：本HIV-艾滋病及相关疾病研究合作（FIRCA）申请提出的研究将加强美国俄亥俄州州立大学（帕特里克绿色博士）和意大利帕多瓦大学（Donna D 'Agostino博士）两个高产研究小组之间新开发的合作。主要研究者参加了2001年6月25-29日在爱尔兰的都柏林举行的“第10届人类逆转录病毒学国际会议：HTLV和相关病毒”，随后，参与实验室之间的联合研究项目出现。会议期间，讨论了以下提案中概述的联合项目。要继续进行这些富有成效的交流，关键是要有资金，使合作能够成熟，以利于美国调查人员，并扩大意大利帕多瓦大学实验室的研究能力。拟议的研究将联合收割机结合在每个机构建立的资源，用于两个参与者的集体利益。HIV和HTLV是复杂的逆转录病毒，其表达由病毒调节蛋白达特和Rev（HIV）以及Tax和雷克斯（HTLV）控制。我们的研究实验室一起进行了基础研究，以确定每种病毒的调节蛋白的作用，并处于独特的位置，以确定这些类似的调节蛋白如何影响这些复杂逆转录病毒的基因表达和复制。绿色博士的研究小组已经表明，税收是必不可少的细胞转化，并确定了一个新的磷酸化结构域的雷克斯-2，调节其功能。D 'Agostino博士表明，通过替代性剪接，HTLV-2可能会产生截短形式的雷克斯-2，称为x-III蛋白，充当全长雷克斯-2的抑制子。最近，她的团队证明了Rev中一个环区域的功能重要性，该区域影响了对其功能至关重要的蛋白质的几个特性。具体的目标，将在我们提出的合作研究是：1）探索磷酸化的作用，在活动的x-III蛋白和检查其对HTLV-2复制的影响;和2）调查的控制Rev的构象和功能的蛋白激酶C介导的磷酸化丝氨酸残基和异构化的脯氨酸在环区。拟议中的艾滋病相关FIRCA汇集的综合设施和专业知识是独特的，富有成效的，并履行福格蒂国际中心支持美国和外国之间合作研究的使命。

DESCRIPTION (provided by applicant): The present HIV-AIDS and Related Illnesses Research Collaboration (FIRCA) application proposes studies that will strengthen a newly developed collaboration between two highly productive research groups at The Ohio State University, USA (Dr. Patrick Green) and the University of Padova, Italy (Dr. Donna D'Agostino). Joint research projects between the participating laboratories emerged following the principal investigators' participation in the "10th International Conference on Human Retrovirology: HTLV and Related Viruses held in Dublin, Ireland, June 25-29, 2001. During the meeting, joint projects were discussed as outlined in the following proposal. Critical to the continuation of these productive exchanges are funds to allow the collaborations to mature for the benefit of the United States investigator and to enable expansion of the research capacity of the laboratory at the University of Padova, Italy. The proposed research will combine the resources that are established in each institution to be used for the collective benefit of both participants. HIV and HTLV are complex retroviruses whose expression is controlled by the viral regulatory proteins Tat and Rev (HIV) and Tax and Rex (HTLV). Together, our research laboratories have performed basic studies to define the role of regulatory proteins of each virus and are in a unique position to determine how these analogous regulatory proteins influence gene expression and replication of these complex retroviruses. Dr. Green's research group has shown that Tax is essential for cellular transformation and has identified a novel phosphorylation domain of Rex-2 that regulates its function. Dr. D'Agostino has shown that, through altemative splicing, HTLV-2 may produce truncated forms of Rex-2 termed x-III proteins that act as repressors of full-length Rex-2. More recently, her group demonstrated the functional importance of a loop region in Rev that influences several properties of the protein that are essential to its function. Specific aims that will be addressed in our proposed collaborative research are: 1) to explore the role of phosphorylation in the activity of the x-III proteins and examine their effect on HTLV-2 replication; and 2) to investigate the control of Rev's conformation and function by protein kinase C-mediated phosphorylation at serine residues and by isomerization of prolines in the loop region. The combined facilities and expertise brought together by the proposed AIDS-related FIRCA are unique, productive, and fulfill the mission of the Fogarty International Center to support collaborative research between the United States and foreign countries.