Function of the gammaHV68 M2 Antigen

gammaHV68 M2 抗原的功能

• 批准号: 6987789
• 负责人: SAMUEL H SPECK
• 金额: $ 37.13万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6987789
• 关键词: B cell receptor; B lymphocyte; Epstein Barr virus; Gammaherpesvirinae; Herpesviridae disease; Kaposi' s sarcoma; T lymphocyte; antibody; binding proteins; biological signal transduction; cell differentiation; cell proliferation; disease /disorder model; epidermal growth factor; genetically modified animals; growth factor receptors; host organism interaction; humoral immunity; laboratory mouse; laboratory rabbit; latent virus infection; protein protein interaction; protein structure function; receptor binding; virus antigen; virus protein

DESCRIPTION (provided by applicant): Gammaherpesviruses are closely associated with the development of lymphoproliferative disease and lymphomas, as well as other cancers. The long-term goal of this research is to understand how gammaherpesviruses manipulate normal B or T cell development to persist within the lymphoid compartment of the infected host. Understanding the mechanisms used by gammaherpesviruses to persist in the infected host may lead to the development of strategies for interfering with chronic infection. The focus of the proposed studies on murine gammaherpesvirus 68 (gHV68; also referred to as MHV-68) represents an ongoing effort to develop a tractable small animal model for characterizing establishment and maintenance of gammaherpesvirus infection. The proposed studies focus on the determining the function of one of the critical latency-associated antigens of gHV68, the M2 antigen. Aim 1. In vivo characterization of gHV68 M2 mutant viruses, 1.a. Role of M2 antigen in the establishment of latency in specific B cell reservoirs; 1.b. Characterization of M2 mutant virus reactivation from B cells in response to a define stimulus; 1.c. Generation of M2-deficient mutants on a replication defective background; and 1.d. Adoptive transfer of gHV68 latently infected naive and memory B cells into uninfected recipient mice. Aim 2. Characterization of gHV68 M2 B cell transgenic mice. 2.a. Generation and initial characterization of M2 B cell transgenic mice; and 2.b. Characterization of B cell development and responses in M2 B cell transgenic mice. Aim 3. Identify and characterize interactions of the M2 antigen with cellular proteins. 3.a. Characterization of M2 antigen interaction with endophilin II and Grb2 in mammalian cells; 3.b. Generation and characterization of M2 mutant viruses that disrupt the interaction of M2 with endophilin II and/or Grb2; and 3.c. Characterization of the impact of M2 antigen expression on growth factor receptor and B cell receptor internalization and signaling.

描述（由申请人提供）：伽马病毒与淋巴增生性疾病和淋巴瘤以及其他癌症的发展密切相关。这项研究的长期目标是了解伽马病毒如何操纵正常的B或T细胞发育以持续在受感染宿主的淋巴区室内。了解γ掌病毒在感染宿主中持续存在的机制可能会导致开发干扰慢性感染的策略。拟议的关于鼠伽马病毒68（GHV68;也称为MHV-68）的研究的重点是开发一种可拖动的小动物模型的持续努力，用于表征γ掌病毒感染的建立和维持。拟议的研究集中于确定M2抗原GHV68的临界潜伏相关抗原之一的功能。 AIM 1。ghv68 m2突变病毒的体内表征，1.a。 M2抗原在特定B细胞库中的潜伏期中的作用； 1.B.响应定义刺激的B细胞的M2突变病毒重新激活的表征； 1.C.在复制有缺陷的背景下生成M2缺陷突变体；和1.D. ghv68的继产传递，潜在地感染了幼稚的和记忆B细胞为未感染的受体小鼠。 AIM 2。GHV68M2 B细胞转基因小鼠的表征。 2.A. M2 B细胞转基因小鼠的产生和初始表征；和2.b。 M2 B细胞转基因小鼠中B细胞发育和反应的表征。目标3。识别并表征M2抗原与细胞蛋白的相互作用。 3.A. M2抗原与哺乳动物细胞中内菲林II和GRB2相互作用的表征； 3.B. M2突变病毒的产生和表征，这些病毒破坏了M2与内菲林II和/或GRB2的相互作用；和3.C. M2抗原表达对生长因子受体和B细胞受体内在化和信号传导的影响的表征。