Retrovirus Budding and Endosomal Sorting

逆转录病毒出芽和内体分选

• 批准号: 8552818
• 负责人: eric freed
• 金额: $ 52.23万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8552818
• 关键词: Amino Acids; Area; Binding; Cells; Complex; Equine Infectious Anemia Virus; Feline Immunodeficiency Virus; Gagging; Goals; HIV Drug Resistance Program; HIV-1; MTCH1 gene; Play; Process; Protein Precursors; Proteins; Reporting; Retroviridae; Role; SNAP receptor; Site Visit; Sorting - Cell Movement; Subfamily lentivirinae; alanylproline; inhibitor/antagonist; particle; prolyl-proline; tyrosyl-proline

The release of retrovirus particles from the infected cell is greatly stimulated by "late" domains present within the Gag precursor protein. Three distinct retroviral late-domain sequences have been identified: Pro-Thr/Ser-Ala-Pro (PTAP or PSAP), Pro-Pro-X-Tyr (PPXY, where X is any amino acid), and Tyr-Pro-Xn-Leu (YPXnL). We played a key early role in identifying the PTAP late domain of HIV-1, and, along with other labs, contributed to the discovery that late domains function by interacting with components of the endosomal sorting complex required for transport (ESCRT) machinery. We continue to be actively involved in elucidating the host cell machinery required for the release of HIV-1 and other lentiviruses (e.g., EIAV and FIV) and are in the process of identifying inhibitors of retrovirus budding. Much of our recent effort in this area is focused on the role of Alix in HIV-1 budding and cell-cell transfer.[Corresponds to Freed Project 2 in the October 2011 site visit report of the HIV Drug Resistance Program]

GAG前体蛋白中存在的“晚期”结构域极大地刺激了逆转录病毒颗粒从感染细胞中的释放。已鉴定出三个不同的逆转录病毒晚期结构域序列：Pro-Thr/Ser-Ala-Pro(PTAP或PSAP)、Pro-Pro-X-Tyr(PPXY，其中X是任何氨基酸)和Tyr-Pro-Xn-Leu(YPXnL)。我们在确定HIV-1的PTAP晚期结构域方面发挥了关键的早期作用，并与其他实验室一起，通过与运输所需的内体分选复合体(ESCRT)机制的组件相互作用而促进了这一发现。我们继续积极参与阐明释放HIV-1和其他慢病毒(如EIAV和FIV)所需的宿主细胞机制，并正在寻找逆转录病毒萌芽的抑制剂。我们最近在这一领域的大部分工作都集中在Alix在HIV-1萌芽和细胞间转移中的作用。