SEMEN IN TRANSMISSION OF HIV

精液传播艾滋病毒

• 批准号: 8099994
• 负责人: Phalguni GUPTA
• 金额: $ 10.85万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8099994
• 关键词: Address; Affect; Biological Assay; Biological Factors; Blood; Blood specimen; Cells; Cloning; Cultured Cells; Data; Detection; Disease; Dominican Republic; Drug resistance; Evolution; Female; Genes; Genotype; HIV; HIV-1; HIV-1 load; Heterosexuals; Immune; In Situ; Leukocytes; Location; Lymphocyte; Male Genital Organs; Measures; Metabolic Clearance Rate; Methods; Nucleotides; Phenotype; Plasma; Polymerase; Population; Prostate; Protease Gene; Puerto Rico; Research; Research Personnel; Resources; Sampling Studies; Seminal; Seminal Plasma; Seminal Vesicles; Seminal fluid; Sexual Transmission; Site; Source; Testis; Time; Tissue Sample; Tissues; Urethra; Variant; Vas deferens structure; Viral; Viral Load result; antiretroviral therapy; cell type; experience; male; men; pressure; programs; receptor; response; transmission process; viral RNA

DESCRIPTION (provided by applicant): Cell-free and cell-associated HIV-1 have been detected in semen from HIV-1-infected subjects. HIV-1 populations in semen have been shown to be different than those in blood of most infected subjects. We have recently demonstrated that the HIV-1 population in semen is further subcompartmentalized between seminal leukocytes and seminal plasma. Furthermore, HIV-1 in these two seminal subcompartments may originate from different anatomical sites of the male genital tract. However, there is no information available whether transmission occurs via cell-free or cell-associated HIV-1 or both present in semen. Compartmentalization of HIV-1 between seminal cells and seminal plasma raises the possibility that the viral dynamics in these two seminal compartments are different. Therefore, the responses of cell-free and cell- associated HIV-1 in semen to antiretroviral therapies could be different. Our overall hypothesis is that HIV- 1 in male genital organ is highly compartmentalized and this Compartmentalization can affect transmission and is sensitivity to therapy. To address these hypotheses we propose the following specific aims: 1) To determine whether cell-free or cell-associated HIV-1 in semen is involved in heterosexual transmission by analyzing the HIV-1 envelope gene from seminal cells and seminal plasma from transmitting men with and without therapy, and blood from their infected female partners soon after exposure; 2) To investigate on the effect of short-term and long-term therapy on cell-associated and cell-free HIV-1 in semen. Clearance rate of cell-free and cell-associated HIV-1 in semen and blood will be measured during the short-term therapy by measuring viral load at short intervals before and after therapy. Long term therapy (more than 2 years) will be used to determine whether antiretroviral therapy has a differential effect on the viral reservoir in cell-free compartment as compared to cell-associated compartment in semen and blood. This will be done by measuring viral expression in cultured cells and HIV-1 evolution; 3) To determine the anatomical location of HIV-1 in the male genital organ and evaluate the effect of antiretroviral therapy on HIV- 1 in the various male genital tissues. The level of viral RNA in prostate, seminal vesicle, testes, vas-deference and urethra in HIV-1-infected subjects before and after therapy will be measured. We have assembled all the resources and expertise to accomplish the stated specific aims in this proposal. Semen and blood sample for studies described in Aims 1 and 2 will be obtained from HIV infected subjects from Dominican republic and Puerto Rico though our ongoing collaborative studies. Tissue sample for Aim 3 will be obtained from the National Disease Research Interchange (NDRI).The information from the proposed study will be extremely useful to our understanding of transmission and eradication of HIV-1 following therapy.

描述（由申请人提供）：已在 HIV-1 感染者的精液中检测到无细胞和细胞相关的 HIV-1。研究表明，大多数感染者精液中的 HIV-1 群体与血液中的 HIV-1 群体不同。我们最近证明，精液中的 HIV-1 群体进一步分为精浆白细胞和精浆。此外，这两个精囊室中的 HIV-1 可能源自男性生殖道的不同解剖部位。然而，尚无可用信息表明传播是通过精液中存在的无细胞HIV-1还是细胞相关HIV-1或两者同时发生。 HIV-1 在精细胞和精浆之间的区室化提出了这两个精室中的病毒动力学不同的可能性。因此，精液中的无细胞和细胞相关HIV-1对抗逆转录病毒治疗的反应可能不同。我们的总体假设是，男性生殖器官中的 HIV-1 是高度区室化的，这种区室化可以影响传播并对治疗敏感。为了解决这些假设，我们提出以下具体目标： 1) 通过分析来自传播者精细胞和精浆的 HIV-1 包膜基因，确定精液中的无细胞或细胞相关 HIV-1 是否参与异性传播经过或未经治疗，以及接触后不久被感染的女性伴侣的血液； 2) 研究短期和长期治疗对精液中细胞相关和游离HIV-1的影响。在短期治疗期间，将通过在治疗前后的短时间内测量病毒载量来测量精液和血液中无细胞和细胞相关 HIV-1 的清除率。长期治疗（超过 2 年）将用于确定抗逆转录病毒治疗对精液和血液中无细胞区室中的病毒库与细胞相关区室中的病毒库是否有不同的影响。这将通过测量培养细胞中的病毒表达和 HIV-1 进化来完成； 3) 确定HIV-1在男性生殖器官中的解剖位置，并评估抗逆转录病毒治疗对各种男性生殖组织中HIV-1的影响。将测量治疗前后HIV-1感染者的前列腺、精囊、睾丸、输精管和尿道中的病毒RNA水平。我们汇集了所有资源和专业知识来实现​​本提案中规定的具体目标。通过我们正在进行的合作研究，目标 1 和 2 中描述的研究的精液和血液样本将从多米尼加共和国和波多黎各的 HIV 感染受试者中获得。目标 3 的组织样本将从国家疾病研究交流中心 (NDRI) 获得。拟议研究的信息对于我们了解治疗后 HIV-1 的传播和根除非常有用。

项目成果

Evaluation of cervical mucosa in transmission bottleneck during acute HIV-1 infection using a cervical tissue-based organ culture.

使用基于宫颈组织的器官培养评估急性 HIV-1 感染期间宫颈粘膜传播瓶颈。

• 发表时间: 2012
• 影响因子: 3.7
• 作者: Shen, Chengli;Ding, Ming;Ratner, Deena;Montelaro, Ronald C;Chen, Yue;Gupta, Phalguni
• 通讯作者: Gupta, Phalguni

Study of HIV-1 transmission across cervical mucosa to tonsil tissue cells using an organ culture.

使用器官培养研究 HIV-1 通过宫颈粘膜传播至扁桃体组织细胞。

• 发表时间: 2013-01
• 作者: Soto;Patterson, Bruce K;Chen, Yue;Shen, Chengli;Ratner, Deena;Ding, Ming;Tumne, Ashwin;Gupta, Phalguni
• 通讯作者: Gupta, Phalguni