FUNCTION FOR VPR AND VPX OF PRIMATE LENTIVIRUSES

灵长类慢病毒的 VPR 和 VPX 功能

• 批准号: 2074225
• 负责人: Mario Stevenson
• 金额: $ 16.19万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2074225
• 关键词: FUNCTION; VPR; VPX; PRIMATE; LENTIVIRUSES

DESCRIPTION (adapted from the Abstract): The CD4+ T cells and macrophages represent the primary targets for infection with HIV-1. Replication of HIV-1 within macrophages plays a fundamental role in virus transmission, in the sequestration of HIV-1 in tissues, and in the maintenance of HIV-1 persistence during the progression of disease. Although macrophages are terminally differentiated and non-dividing cells, mitosis is not required for productive infection by lentiviruses, such as HIV-1, in contrast to onco-retroviruses which do require host cell mitosis for nuclear localization of viral DNA and provirus establishment. The infection of non-dividing cells by HIV-1 is governed by the association of virion-derived nucleophilic proteins with the viral genome, which facilitate nuclear localization of the viral genome in non-dividing cells. The Principal Investigator and his associates have shown that the nucleophilic virion protein Vpr remains associated with viral nucleic acids after virus infection and, as a consequence, facilitates nuclear localization of viral DNA in non-dividing cells. In this project, the Investigator proposes to characterize the mechanism by which Vpr and the related virion protein Vpx of HIV-2 and SIV determine nuclear localization of viral DNA and establish the provirus in non-dividing host cells. He and his associates will: (1) characterize determinants which govern nuclear localization of Vpr and Vpx and derive infectious molecular clones of HIV-1 and HIV-2 containing amino acid substitutions which preclude nuclear localization of Vpr and Vpx; (2) examine the replication phenotype of HIV-1 Vpr and HIV-2 Vpr/Vpx nuclear localization mutants in primary lymphocytes and macrophages, and the role of these proteins in nuclear targeting of viral DNA and in provirus establishment in these cell systems; and (3) identify the virion factors necessary for association of Vpr and Vpx with viral nucleic acids within the viral nucleoprotein preintegration complex.

描述（根据摘要改编）：CD4+ T细胞和 巨噬细胞代表感染HIV-1的主要靶标。 巨噬细胞中HIV-1的复制在 病毒传播，在组织中HIV-1的隔离中 在疾病进展过程中维持HIV-1的持久性。 尽管巨噬细胞是最终区分和非分明的 细胞，慢病毒的生产性感染不需要有丝分裂， 例如HIV-1，与确实需要宿主的Onco-Retrovirus相比 病毒DNA和病毒病毒核定位的细胞有丝分裂 建立。 HIV-1的非分裂细胞感染受到控制 通过衍生的亲核蛋白与 病毒基因组，促进病毒基因组的核定位 在非分散细胞中。 首席调查员及其同事 已经表明亲核病毒体蛋白VPR仍然相关 病毒感染后病毒核酸，因此 促进病毒DNA在非分散细胞中的核定位。 在这个项目中，调查人员提议表征机制 通过哪种HIV-2和SIV的VPR和相关的病毒蛋白VPX 确定病毒DNA的核定位并建立病毒 在非分裂的宿主细胞中。 他和他的同事将：（1） 表征了统治VPR核定位的决定因素和 VPX和含有HIV-1和HIV-2的传染性分子克隆 排除VPR和VPR核定位的氨基酸取代 VPX; （2）检查HIV-1 VPR和HIV-2的复制表型 初级淋巴细胞中的VPR/VPX核定位突变体 巨噬细胞，以及这些蛋白质在病毒的核靶向中的作用 在这些细胞系统中的DNA和原病毒建立； （3） 确定VPR和VPX关联所必需的病毒因素 病毒核酸在病毒核蛋白前融合内的核酸 复杂的。