FUNCTIONAL STUDIES WITH HYBRID HIVS

混合型 HIV 的功能研究

• 批准号: 3144035
• 负责人: Alagarsamy Srinivasan
• 金额: $ 19.95万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-11-01 至 1994-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3144035
• 关键词: endonuclease; genetic manipulation; genetic recombination; helper T lymphocyte; human immunodeficiency virus; human tissue; lymphocyte; molecular cloning; monocyte; nucleic acid repetitive sequence; protein structure; provirus; restriction endonucleases; tissue /cell culture; transfection; virus DNA; virus cytopathogenic effect; virus genetics; virus protein; virus replication

The etiologic agent of acquired immunodeficiency syndrome (AIDS) is the human immunodeficiency virus (HIV). HIV is a genomically and biologically heterogeneous virus; many reports have noted that a wide variety of HIV strains exist with differing nucleotide sequences and widely differing biological properties. Differential replication of HIV isolates in vitro has been reported in established lines of T cells, B cells, monocytes and in PHA stimulated PBL. Recent studies demonstrate that many HIV variants exists within an infected individual at any one time and that the clinical condition of the patient correlates with the collective biological properties of those viruses in vitro. Although it is speculated that the differences in replication kinetics of HIV isolates are determined by differences in the viral nonstructural proteins and the control elements of the LTR, the viral determinants responsible for differential replication, tropism and cytopathic effects are not known. If the biological diversity in vitro has relevance to replication in vivo, an understanding of the genetic factors that govern the biological properties of the virus would contribute to efforts in controlling pathogenicity. To determine the regions of the viral genome responsible for the differential replication, tropism and cytopathic effects of HIVs, a series of hybrid viruses will be constructed from molecular clones of several well characterized HIV isolates. The replication potential, tropism and cytopathogenicity of the hybrid and parental viruses will be determined in a variety of cells. The long term objective is to understand the molecular basis of the distinctive biological properties of HIVS.

获得性免疫缺陷综合征（艾滋病）的病原体是 人类免疫缺陷病毒（HIV）。 艾滋病病毒是一种基因组和生物学 许多报告指出，各种各样的艾滋病毒 存在具有不同核苷酸序列的菌株， 生物学特性 HIV分离株的体外差异复制 已报道在T细胞、B细胞、单核细胞和 PHA刺激的PBL。 最近的研究表明，许多艾滋病毒变种 在任何时候都存在于受感染的个体中，并且临床 患者的状况与集体生物学 这些病毒在体外的特性。 虽然据推测， HIV分离株复制动力学的差异由以下决定： 病毒的非结构蛋白和控制元件的差异 LTR，负责差异复制的病毒决定簇， 向性和细胞病变效应尚不清楚。 如果生物多样性 体外复制与体内复制有关， 控制病毒生物学特性的遗传因素 有助于控制致病性的努力。 确定 负责差异复制的病毒基因组区域， 由于HIV病毒的嗜性和致细胞病变作用， 由几种已充分表征的HIV的分子克隆构建而成 分离株 的复制潜力、嗜性和致细胞病变性。 将在多种细胞中测定杂交病毒和亲本病毒。 的 长期目标是了解不同的分子基础， HIV的生物学特性。