FUNCTIONAL STUDIES WITH HYBRID HIVS

混合型 HIV 的功能研究

• 批准号: 3144036
• 负责人: Alagarsamy Srinivasan
• 金额: $ 20.31万
• 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/3144036
• 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症（艾滋病）的病因是 人类免疫缺陷病毒（HIV）。 HIV是一种基因组学和生物学上的病毒 异质病毒；许多报告指出，多种艾滋病毒 菌株存在不同的核苷酸序列并且差异很大 生物学特性。 HIV分离株的体外复制差异 据报道，已建立的 T 细胞、B 细胞、单核细胞和 在 PHA 刺激的 PBL 中。 最近的研究表明，许多 HIV 变种 任何时候都存在于受感染个体体内，并且临床上 患者的状况与集体生物学相关 这些病毒的体外特性。 尽管有人猜测 HIV分离株复制动力学的差异由以下因素决定 病毒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因素， 向性和细胞病变效应尚不清楚。 如果生物多样性 体外与体内复制相关，了解 控制病毒生物学特性的遗传因素 为控制致病性做出贡献。 确定 病毒基因组中负责差异复制的区域， HIV的趋向性和细胞病变效应，一系列混合病毒将被 由几个已明确表征的 HIV 的分子克隆构建 隔离。 复制潜力、向性和致细胞病变性 杂交病毒和亲本病毒将在多种细胞中进行测定。 这 长期目标是了解独特的分子基础 HIVS 的生物学特性。