PROPHYLAXIS OF FETAL HEMATOPOIETIC CELLS FOR FIV

胎儿造血细胞的五次预防

• 批准号: 6510797
• 负责人: AYALEW MERGIA
• 金额: $ 26.77万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6510797
• 关键词: AIDS; AIDS therapy; cats; disease /disorder model; feline immunodeficiency virus; gene therapy; hematopoietic stem cells; nucleic acid sequence; polymerase chain reaction; restriction fragment length polymorphism; ribozymes; technology /technique development; tissue /cell culture; transfection

DESCRIPTION: Human immunodeficiency virus (HIV) has an extraordinary survival advantage, confounding existing therapies. With a short generation time, variable antigenicity, and a large number of infective virions, it is hardly surprising that despite the development of anti-viral pharmaceutical compounds, we have managed to only delay the onset of the fatal acquired immunodeficiency syndrome (AIDS). Novel antiviral therapy, specifically the insertion of genes which endow lymphohematopoietic cells with life-long protection against lentivirus infections offers a fresh approach to combating HIV infection. To date, the utility of this therapy has been hampered by the small number of hematopoietic stem cells available for transfection. We are poised to overcome these impediments by using a virtually limitless source of fetal hematopoietic cells (FHC) which are rich in immunologically-naive stem cells. By increasing the cell target numbers for transfection and transplantation we will be able to more rapidly determine the efficacy of stem cell gene therapy for treatment lentivirus infection. The animal model system we will employ is the feline immunodeficiency virus (FIV) in cats. FIV is a naturally-occurring retrovirus of domestic cats that provides valuable resources for understanding mechanisms of pathogenesis and for development of effective antiviral therapy and vaccines with direct relevance to HIV. The current proposal is to develop ribozyme based antiviral gene therapy against FIV infection in cats by targeting the regulatory gene rev and its cognate recognition sequences, rev response element (RRE), which are critical for virus replication. Antiviral sequences against rev and RRE will be delivered into cats using retroviral vectors by way of FHC. The long term goal of this research is to use this animal-model of HIV infection to determine whether decreasing retrovirus burden by myeloablation of a life-long source of blood cells, which are prophylactically protected against retrovirus infection, might provide a new therapy for individuals infected with HIV.

描述：人类免疫缺陷病毒（HIV）具有非凡的 生存优势，混淆现有疗法。 用短短的一代人 时间，可变的抗原性和大量的感染性病毒体， 尽管抗病毒药物的发展， 化合物，我们已经设法只延迟致命的获得性 免疫缺陷综合征（艾滋病）。 新的抗病毒疗法，特别是 基因的插入，赋予淋巴造血细胞终身 针对慢病毒感染的保护提供了一种新的方法， 防治艾滋病毒感染。 到目前为止，这种疗法的效用已经 造血干细胞的数量很少， 转染 我们准备通过使用 几乎无限的胎儿造血细胞（FHC）来源， 在免疫幼稚干细胞中。 通过增加细胞目标数量 对于转染和移植，我们将能够更快地 确定干细胞基因疗法治疗慢病毒的疗效 感染 我们将采用的动物模型系统是猫 免疫缺陷病毒（FIV）在猫。 FIV是一种自然发生的 家猫的逆转录病毒，提供宝贵的资源， 了解发病机制和发展有效的 抗病毒治疗和疫苗与艾滋病毒直接相关。 当前 提出了一种基于核酶的抗FIV基因治疗方法 通过靶向调节基因rev及其同源基因在猫中的感染 识别序列，转速响应元件（RRE），这是至关重要的 病毒复制 针对rev和RRE的抗病毒序列将被 通过FHC的方式使用逆转录病毒载体递送到猫中。 长期 这项研究的目的是利用这种艾滋病毒感染的动物模型， 确定是否通过骨髓消融降低逆转录病毒负荷， 血细胞的终身来源，受到免疫保护 抗逆转录病毒感染，可能为个体提供一种新的治疗方法， 感染了艾滋病病毒

项目成果

Viral gene expression and provirus load of Orf-A defective FIV in lymphoid tissues and lymphocyte subpopulations of neonatal cats during acute and chronic infections.

急性和慢性感染期间新生猫淋巴组织和淋巴细胞亚群中 Orf-A 缺陷 FIV 的病毒基因表达和原病毒载量。

• DOI: 10.1016/j.virusres.2007.06.001
• 发表时间: 2007
• 期刊: Virus research
• 影响因子: 5
• 作者: Novak,JanelleM;Crawford,PCynthia;Kolenda-Roberts,HollyM;Johnson,CalvinM;Mergia,Ayalew
• 通讯作者: Mergia,Ayalew

Hematopoiesis in the feline fetal liver: an assessment by flow cytometry.

猫胎儿肝脏中的造血作用：通过流式细胞术进行评估。

• DOI: 10.1016/j.vetimm.2004.01.007
• 发表时间: 2004
• 期刊: Veterinary immunology and immunopathology.
• 作者: Johnson,CalvinM;Gengozian,Nazareth;Mergia,Ayalew
• 通讯作者: Mergia,Ayalew