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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 HIV-1感染最常通过性接触获得，全世界HIV-1的性传播大多数是异性性接触的结果。 育龄妇女感染HIV-1的风险最大，导致全世界妇女、新生儿和婴儿感染HIV-1的人数相应增加。 然而，尽管性传播在HIV-1的持续传播中占主导地位，但对妇女通过性传播HIV-1的机制仍然知之甚少。 例如，目前尚不清楚无细胞病毒、细胞相关病毒或两者是否是HIV-1在人类中传播所必需的。 HIV-1跨粘膜上皮传播的潜在机制包括1）上皮细胞的直接感染; 2）通过上皮细胞和/或特化微折叠（M）细胞的转胞吞作用; 3）受感染供体细胞的上皮迁移; 4）上皮内朗格汉斯细胞的摄取和5）通过物理破坏绕过上皮屏障。 病毒成功转移穿过上皮屏障可能导致HIV-1被迁移性树突状细胞（通过DC-SIGN或另一种甘露糖C型凝集素受体）摄取，随后扩散至引流淋巴结和/或局部粘膜HIV-1感染，导致招募额外的易感细胞。尽管许多问题仍未得到解答，但这些调查揭示了预防妇女艾滋病毒传播的潜在目标，这对限制全球艾滋病流行至关重要。