Characterization of Exosomes From Semen of Uninfected and HIV-Infected Men

未感染和 HIV 感染男性精液中外泌体的表征

• 批准号: 9062790
• 负责人: Nadia R Roan
• 金额: $ 25.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9062790
• 关键词: AIDS/HIV problem; Acute; Affect; Amyloid; Attention; CD4 Positive T Lymphocytes; Cell Line; Cells; Data; Data Set; Disease; Endometrial; Enrollment; Epithelial; Epithelial Cells; Epithelium; Event; Exposure to; Female; Flow Cytometry; Genetic Transcription; Genital system; HIV; HIV Infections; HIV-1; Immune; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Interleukin-6; Lead; Lipids; Liquid substance; Mediating; Mucous Membrane; Plasma; Play; Predisposition; Pregnancy; Production; Property; Prostaglandins; Proteins; RNA; Recruitment Activity; Role; Sampling; San Francisco; Seminal; Seminal Plasma; Seminal fluid; Sexually Transmitted Diseases; Signal Transduction; Source; Staging; TNF gene; Testing; Time; Transducers; Transforming Growth Factor beta; Vesicle; Viral Load result; Work; cellular targeting; chemokine; cohort; comparative; cytokine; exosome; extracellular vesicles; in vivo; macrophage; men; pathogen; public health relevance; release factor; reproductive tract; response; sexual HIV transmission; sperm cell; transcriptome sequencing; transcriptomics; transmission process

 DESCRIPTION (provided by applicant): The continuing spread of HIV/AIDS in people is predominantly fueled by sexual exposure to HIV-contaminated semen/seminal plasma (SP). SP harbors a variety of pro-inflammatory factors that may facilitate HIV transmission by promoting the production of cytokines/chemokines that recruit permissive cells, enhance the translocation of HIV across the genital epithelium, and activate HIV gene transcription. The levels of these factors have been shown to be altered during HIV infection, with HIV-infected individuals generally harboring higher levels of various pro-inflammatory cytokines in SP. We and others have extensively studied the properties of SP constituents, both with regards to their ability to promote HIV infection and their ability to create an inflammatory state favoring HIV replication. However, one class of factors in SP that has received little attention is exosomes, small extracellular vesicles of which trillions are typically present in a single ejaculate. Exosomes are important intercellular signal transducers and induce various inflammatory or immunomodulatory responses. Although numerous studies have characterized plasma-derived exosomes from both uninfected and HIV-infected individuals, very little has been done to understand the relationship between semen exosomes and HIV transmission. In this R21, we test the hypotheses that HIV infection alters the composition of exosomes in SP and that SP exosomes from HIV-infected men can induce inflammation and promote susceptibility to HIV infection. We will accomplish this by assessing in Aim 1 how HIV infection and ART treatment status affect the quantity, composition, and RNA cargo of exosomes in SP. Then in Aim 2, we will directly test the whether exosomes from HIV-infected men contribute towards the ability of SP to induce inflammation in cells lining the genital mucosa, and whether these exosomes can increase the susceptibility of permissive cells to HIV infection. These studies will be the first t characterize SP exosomes from HIV-infected men, and will lead to a better understanding of how these vesicles affect the early events of sexual transmission of HIV.

 描述（由适用提供）：艾滋病毒/艾滋病在人们中的持续传播主要是由于性暴露于艾滋病毒污染的精液/精液等离子体（SP）的范围。 SP具有多种促炎性因子，这些因素可能通过促进募集允许细胞的细胞因子/趋化因子的产生来促进HIV传播，从而增强HIV跨越生殖器上皮的易位并激活HIV基因转录。这些因素的水平已显示在HIV感染期间会改变，而感染HIV的个体通常具有SP的各种促炎性细胞因子的较高水平。我们和其他人都广泛研究了SP构成的特性，这既取决于它们促进HIV感染的能力及其创造有利于HIV复制的炎症状态的能力。但是，SP中的一类因素很少受到关注，外泌体是一个射精中通常存在的小细胞外蔬菜。外泌体是 重要的细胞间信号传感器，并诱导各种炎症或免疫调节反应。尽管许多研究表征了来自未感染和HIV感染的个体的血浆衍生的外泌体，但几乎没有做到了解精液外泌体和HIV传播之间的关系。在此R21中，我们检验了HIV感染改变SP中外泌体的组成的假设，而来自HIV感染的男性的SP外泌体可以诱导感染并促进对HIV感染的敏感性。我们将通过在AIM 1中评估HIV感染和艺术治疗状况如何影响SP中外泌体的数量，组成和RNA货物来实现这一目标。然后，在AIM 2中，我们将直接测试来自HIV感染的男性的外泌体是否有助于SP在生殖器粘膜内诱导细胞中感染的能力，以及这些外泌体是否可以增加允许细胞对HIV感染的敏感性。这些研究将是第一个表征来自HIV感染男性的SP外泌体的研究，并将更好地了解这些蔬菜如何影响HIV的性传播的早期事件。