MECHANISMS FOR HIV-1 PERSISTENCE IN HUMAN MAMMARY TISSUE AND BREAST MILK CELLS

HIV-1 在人类乳腺组织和母乳细胞中持续存在的机制

• 批准号: 7720754
• 负责人: Stephanie M Dorosko
• 金额: $ 5.48万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720754
• 关键词: Anti-Retroviral Agents; Apical; Breast Feeding; CD4 Positive T Lymphocytes; Cells; Child; Computer Retrieval of Information on Scientific Projects Database; Conditioned Culture Media; Data; Epithelial; Epithelial Cells; Funding; Grant; HIV; HIV Infections; Highly Active Antiretroviral Therapy; Human; Human Milk; IL8 gene; Infant; Institution; Lymphocyte; Mammary gland; Measures; Milk; Mothers; Prevention; Research; Research Personnel; Resources; Role; Satellite Viruses; Source; Surface; Tissues; Treatment Protocols; United States National Institutes of Health; Virus; abstracting; chemokine; cytokine; feeding; intrapartum; monolayer; research study; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Transmission of HIV during breastfeeding remains the most significant challenge for the prevention of mother-to-child HIV transmission (MTCT) worldwide. Although short-course antiretroviral regimens can reduce transmission to as low as 2-4% during the antenatal and intrapartum periods, these gains may be lost during breastfeeding. Both cell-free and cell-associated virus in breast milk is associated with MTCT. Maternal highly active antiretroviral therapy (HAART) reduces the cell-free source of virus in breast milk, but does not lower cell-associated virus. The broad objective of our current studies is to elucidate the mechanisms by which the mammary gland and breast milk serve as a reservoir for persistence of HIV infection and replication in between infant feedings. Our efforts include investigating the role of cytokines and chemokines secreted from milk-producing cells, also known as mammary epithelial cells (MEC), in inducing recruitment, proliferation, and HIV replication in CD4+ target cells. Our preliminary 27-plex Luminex data showed that IL-8 is highly expressed by both the apical and basolateral surfaces of primary human MEC. With the use of immunomagnetic beads against BerEP4, we isolated and cultured primary MEC on transwell inserts until a tightly polarized epithelial monolayer was achieved. MEC-conditioned media from both the apical and basolateral chambers was utilized in experiments to measure IL-8 concentrations. Our recent data indicates that MEC apically-conditioned media significantly increases both the proliferation of, and HIV replication in, CD4+ T lymphocytes. However, neither apically nor basolaterally conditioned media contributes to lymphocyte recruitment. The studies described in this abstract constitute a portion of the preliminary data that were used in conjunction with the application for our recently-funded NIH K08 grant.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 母乳喂养期间艾滋病毒的传播仍然是全世界预防母亲到孩子艾滋病毒传播（MTCT）的最重大挑战。 尽管短期抗逆转录病毒方案可以在产前和产前时期将传播降低到低至2-4％，但在母乳喂养期间可能会损失这些收益。母乳中无细胞和与细胞相关的病毒都与MTCT有关。 母体高度活性的抗逆转录病毒疗法（HAART）降低了母乳中无细胞病毒的来源，但不会降低与细胞相关的病毒。我们目前研究的广泛目标是阐明乳腺和母乳作为持续性HIV感染和在婴儿喂养之间复制的储层的机制。 我们的努力包括研究牛奶产生细胞（也称为乳腺上皮细胞（MEC））中分泌的细胞因子和趋化因子在CD4+靶细胞中诱导募集，增殖和HIV复制中的作用。我们的初步27-plex luminex数据表明，IL-8由原代人MEC的顶端和基底外侧表面高度表达。通过使用针对BEREP4的免疫磁珠，我们在Transwell插入物上分离并培养的原代MEC，直到达到紧密极化的上皮单层为止。 在实验中使用了来自顶端和基底外侧室的MEC条件培养基来测量IL-8浓度。 我们最近的数据表明，MEC的顶尖介质显着增加了CD4+ T淋巴细胞的增殖和HIV复制。 但是，顶端和基底条件培养基均未促进淋巴细胞募集。 该摘要中描述的研究构成了与我们最近资助的NIH K08 Grant的应用结合使用的初步数据的一部分。