FUNCTIONAL STUDIES WITH HYBRID HIVS

混合型 HIV 的功能研究

• 批准号: 3144038
• 负责人: Alagarsamy Srinivasan
• 金额: $ 23.05万
• 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/3144038
• 关键词: endonuclease; genetic manipulation; genetic recombination; helper T lymphocyte; host organism interaction; 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(AIDS)的病原体是 人类免疫缺陷病毒(HIV)。艾滋病毒是一种基因组和生物学上的 异质病毒；许多报告指出，各种各样的艾滋病毒 菌株存在不同的核苷酸序列和很大的差异 生物学特性。HIV分离株体外差异复制的研究 在已建立的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，许多艾滋病毒变种 在任何时候都存在于感染者体内，并且临床 患者的情况与集体生物学相关 这些病毒的体外特性。尽管据推测， HIV分离株复制动力学的差异由以下因素决定 病毒非结构蛋白及其调控元件的差异 LTR，负责差异复制的病毒决定因素， 趋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相关，理解 控制病毒生物学特性的遗传因素将 有助于控制致病性的努力。要确定 病毒基因组中负责差异复制的区域， HIV的嗜性和细胞病变效应，一系列杂交病毒将被 由几个具有良好特性的HIV的分子克隆构建 分离株。新城疫病毒的复制潜力、趋向性和细胞致病性 杂交病毒和亲本病毒将在各种细胞中确定。这个 长期的目标是了解独特的分子基础 人类免疫缺陷病毒的生物学特性