Core B Cellular Core

核心B项目摘要： 蜂窝核心(核心B)的目标是为该计划项目提供创新和支持 HIV-1Env在由天然HIV-1 Env采样的构象状态背景下的拮抗作用。核心B将 评价小分子拮抗剂对HIV-1感染细胞对抗体依赖的增敏作用 细胞毒性(ADCC)。核心B也将有助于描述小分子环境的作用机制。 三聚体Env上的抑制剂在细胞表面表达。具体而言，核心B将：(A)评估小规模-- 分子环境进入抑制剂使HIV-1感染细胞对ADCC增敏的能力和(B)评估其影响 细胞表面表达的功能性环境三聚体的构象。尽管不是正式的 计划项目在最近的赠款期间，Finzi实验室一直是长期的合作者和 成功地与病毒学(Sodroski)、环肽和多肽仿生学(Chaiken)、小分子相互作用 合成(Smith)和单分子FRET(Moths)项目以促进对环境的理解 感染细胞表面的构象变化，了解环境病毒的构象是如何通过 计划项目产生的不同小分子拮抗剂及其对环境的影响 抗Env抗体和HIV+血清介导的识别和ADCC反应。

Core B Project Summary: The Goal of the Cellular Core (Core B) is to provide innovation and support to this Program Project to investigate HIV-1 Env antagonism in the context of the conformational states sampled by native HIV-1 Env. Core B will evaluate the impact of the small-molecule antagonists on sensitizing HIV-1-infected cells to antibody-dependent cellular cytotoxicity (ADCC). Core B will also help delineate the mechanisms of action of small-molecule Env inhibitors on trimeric Env expressed at the cell surface. Specifically, Core B will: (a) evaluate the ability of small- molecule Env entry inhibitors for their ability to sensitize HIV-1-infected cells to ADCC and (b) assess their impact on the conformation of functional Env trimers expressed on cell surfaces. Despite not being officially part of the Program Project in the most recent grant period, the Finzi laboratory has been a long-term collaborator and successfully interacted with Virology (Sodroski), Cyclic Peptides and Peptidomimetics (Chaiken), Small Molecule Synthesis (Smith), and Single Molecule FRET (Mothes) Projects to advance the understanding of Env conformational changes at the surface of infected cells, understand how Env conformations are modulated by different small-molecule antagonists generated by the Program Project and assess their impact on Env recognition and ADCC responses mediated by anti-Env antibodies and HIV+ sera.