ANTI-HIV-1 TAT HUMAN SFV INTRABODY GENE THERAPY AGAINST SHIV IN RHESUS MACAQUES

抗 HIV-1 TAT 人类 SFV 体内针对恒河猴 SHIV 的基因治疗

• 批准号: 8357904
• 负责人: Wayne A. Marasco
• 金额: $ 6.84万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357904
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; C Type Lectin Receptors; CD209 gene; Cells; Dendritic Cells; Epithelial; Epithelial Cells; Epithelium; Female of child bearing age; Funding; Grant; HIV-1; Heterosexuals; Human; Infection; Investigation; Langerhans cell; M cell; Macaca mulatta; Mannose; National Center for Research Resources; New England; Newborn Infant; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Risk; Satellite Viruses; Sexual Transmission; Source; United States National Institutes of Health; Virus; Woman; base; cost; gene therapy; intraepithelial; lymph nodes; pandemic disease; simian human immunodeficiency virus; transcytosis; transmission process; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. HIV-1 infections are acquired most often through sexual contact, with the majority of the sexual transmission of HIV-1 worldwide occurring as a result of heterosexual contact. Women of childbearing age are at the greatest risk for HIV-1 infection, resulting in a corresponding increase in HIV-1 infection in women, newborns, and infants worldwide. However, despite the predominance of sexual transmission in the continued spread of HIV-1, the mechanisms of sexual transmission of HIV-1 to women are still poorly understood. For example, it is not known whether cell-free virus, cell-associated virus or both are essential for HIV-1 transmission in humans. Potential mechanisms of HIV-1 transmission across mucosal epithelium include 1) direct infection of epithelial cells; 2) transcytosis through epithelial cells and/or specialized microfold (M) cells; 3) epithelial transmigration of infected donor cells; 4) uptake of intraepithelial Langerhans cells and 5) circumvention of the epithelial barrier through physical breaches. Successful transfer of virus across epithelial barriers may result in HIV-1 uptake by migratory dendritic cells (by DC-SIGN or another mannose C-type lectin receptor) and subsequent dissemination to draining lymph nodes and/or localized mucosal HIV-1-infection, leading to recruitment of additional susceptible cells. Although many questions remain unanswered, these investigations have revealed potential targets for prevention of HIV transmission in women which are critical for limiting the global AIDS pandemic.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 HIV-1感染最常通过性接触获得，大部分是由于异性恋接触而发生的HIV-1性传播。 生育年龄的妇女患HIV-1感染的风险最大，导致全世界女性，新生儿和婴儿的HIV-1感染相应增加。 然而，尽管HIV-1继续传播性传播的性传播占主导地位，但HIV-1向女性的性传播机制仍然很少了解。 例如，尚不清楚无细胞病毒，与细胞相关的病毒或两者都是人类HIV-1传播至关重要的。 HIV-1跨粘膜上皮的潜在机制包括1）直接感染上皮细胞； 2）通过上皮细胞和/或专门的微膜（M）细胞的转胞细胞增多； 3）受感染供体细胞的上皮转移； 4）摄取上皮内兰格汉细胞和5）通过物理漏洞规避上皮屏障。 成功地在上皮屏障中转移了病毒可能会导致迁移的树突状细胞（通过DC-SIGN或其他甘露糖C型凝集素受体）的HIV-1摄取，然后随后传播淋巴结和/或局部粘膜HIV HIV-1感染，从而导致其他可感染细胞的募集。尽管许多问题仍未得到解决，但这些调查揭示了预防女性预防艾滋病毒传播的潜在目标，这对于限制全球艾滋病大流行至关重要。