Redox Regulated HIV Expression in Alveolar Macrophages

氧化还原调节肺泡巨噬细胞中的 HIV 表达

• 批准号: 6603000
• 负责人: MICHAEL H IEONG
• 金额: $ 12.77万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6603000
• 关键词: AIDS; HIV infections; alveolar macrophages; antioxidants; bronchoscopy; clinical research; enzyme linked immunosorbent assay; flow cytometry; free radical oxygen; gene expression; high performance liquid chromatography; human immunodeficiency virus 1; human subject; nitrogen; nuclear factor kappa beta; oxidation reduction reaction; oxidative stress; pathologic process; respiratory infections; virus protein; virus replication

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for the development of an academic career in Pulmonary and Critical Care Medicine. The principal investigator has completed a three year residency in Internal Medicine at the University of Maryland and a four year subspecialty training program in Pulmonary and Critical Care Medicine at Boston University (BU). He now seeks to develop his scientific skills of investigation into redox biology and HIV pathogenesis in the lung. Hardy Kornfeld, MD will mentor the principal investigator's development. He is an established investigator and an expert in the area of innate immunity and HIV dynamics in the lung. He has successfully trained graduate students and numerous fellows who are active in academic medicine. Expertise in the area of redox biology will be provided by the co-sponsor Jane Freedman, MD. A committee composed of senior investigators in the areas of redox, HIV and pulmonary biology will meet quarterly with the principal investigator to advise him on scientific and career matters. Research will focus on redox regulation of HIV-1 replication in human alveolar macrophage (AM). Preliminary studies demonstrate inhibition of HIV-1 by reactive oxygen intermediate (ROI) inhibitors at the transcriptional level. The effect of HIV-1 infection and viral proteins on AM production of ROI and reactive nitrogen intermediates (RNI) will be studied. This examination will be extended to naturally infected AM from seropositive individuals to examine the impact of hyperoxia and microbial challenge on redox regulated HIV- 1 replication in AM. The specific aims include: 1 characterizing the effect of HIV on the redox state of AM and its impact on HIV replication dynamics, 2) Determining the mechanism of ROI/RNI induced transcription of HIV, and 3) Determining whether HIV can be induced from naturally infected AM from seropositive patients by altering the redox state. These studies will be the first to analyze the effect of oxidative stress on HIV-1 replication in the human AM, a reservoir of persistent HIV-1 infection in the asymptomatic patient. The Pulmonary Center at BU and The Center for AIDS Research at UMass will provide customized training and outstanding interdisciplinary environments that will support the development of the principal investigators niche in lung biology and facilitate his transition to an independent investigator.

描述（由申请人提供）： 该提案描述了一个为期5年的培训计划，用于发展肺部和重症监护医学的学术生涯。 主要研究者已在马里兰州大学完成了为期三年的内科住院医师培训，并在波士顿大学（BU）完成了为期四年的肺部和重症监护医学专科培训项目。 他现在寻求发展他的科学技能，调查氧化还原生物学和艾滋病毒在肺部的发病机制。 哈代科恩菲尔德，医学博士将指导主要研究者的发展。他是先天免疫和肺部艾滋病毒动力学领域的知名研究者和专家。 他成功地培养了研究生和许多活跃在学术医学领域的研究员。氧化还原生物学领域的专业知识将由共同赞助商Jane Freedman博士提供。 一个由氧化还原、艾滋病毒和肺生物学领域的高级研究人员组成的委员会将每季度与首席研究员举行一次会议，就科学和职业问题向他提供建议。 研究将集中在人类肺泡巨噬细胞（AM）中HIV-1复制的氧化还原调节。 初步研究表明活性氧中间体（ROI）抑制剂在转录水平上抑制HIV-1。 将研究HIV-1感染和病毒蛋白对AM产生ROI和活性氮中间体（RNI）的影响。 这项研究将扩展到自然感染的AM从血清阳性个体检查高氧和微生物的挑战氧化还原调节的HIV- 1复制AM的影响。 具体目标包括：1）表征HIV对AM的氧化还原状态的作用及其对HIV复制动力学的影响，2）确定ROI/RNI诱导HIV转录的机制，和3）确定HIV是否可以通过改变氧化还原状态从来自血清阳性患者的自然感染的AM诱导。 这些研究将首次分析氧化应激对人类AM中HIV-1复制的影响，AM是无症状患者持续HIV-1感染的储存库。 BU的肺中心和麻省大学艾滋病研究中心将提供定制的培训和优秀的跨学科环境，这将支持主要研究者在肺生物学领域的发展，并促进他向独立研究者的过渡。