EFFECTS OF NUCLEOSIDE ANALOGS ON HIV-1 INFECTION OF BRAI

核苷类似物对 BRAI HIV-1 感染的影响

• 批准号: 6394243
• 负责人: AVINDRA NATH
• 金额: $ 21.39万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394243
• 关键词: HIV infections; antiAIDS agent; astrocytes; autoradiography; brain cell; drug interactions; drug screening /evaluation; embryo /fetus tissue /cell culture; gel electrophoresis; human fetus tissue; human immunodeficiency virus 1; hydropathy; immunocytochemistry; lactate dehydrogenases; membrane transport proteins; microglia; nervous system infection; nucleoside analog; pharmacokinetics; phosphorylation; polymerase chain reaction; protein transport; reverse transcriptase inhibitors; sodium; virus cytopathogenic effect

It has been recognized since the beginning of the AIDS epidemic that the brain may be an important reservoir for the human immunodeficiency virus (HIV). Drug development for treatment of HIV infection has progressed to the remarkable pace of two to three drugs being introduced in the clinic every year. However, we currently know very little about their ability to cross the blood brain and brain-cerebrospinal fluid barriers and almost nothing about their ability to enter susceptible cells in the brain, form active metabolites within these cells, or their ability to incorporate into HIV DNA and inhibit its replication. In this proposal we will examine each of six clinically used antiretroviral nucleoside analogs targeted against the reverse transcriptase enzyme and determine their ability to enter human glial cells, to form active metabolites, and to control HIV infection in these cells.

自艾滋病流行以来，人们就认识到大脑可能是人类免疫缺陷病毒（HIV）的重要储存库。用于治疗艾滋病毒感染的药物开发已经取得了惊人的进展，每年有两到三种药物被引入临床。然而，我们目前对它们穿过血脑和脑-脑脊液屏障的能力知之甚少，而且对它们进入大脑中易感细胞、在这些细胞内形成活性代谢物的能力或它们掺入HIV DNA的能力几乎一无所知。并抑制其复制。在本提案中，我们将检查六种临床使用的针对逆转录酶的抗逆转录病毒核苷类似物中的每一种，并确定它们进入人类神经胶质细胞、形成活性代谢物和控制这些细胞中艾滋病毒感染的能力。