Investigation of cellular mechanism of PQBP1-dependant innate signaling of HIV-1

HIV-1 PQBP1 依赖性先天信号传导的细胞机制研究

• 批准号: 318290010
• 负责人: Dr. Renate König
• 金额: --
• 依托单位: Paul-Ehrlich-Institut - Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/318290010?language=en
• 关键词: Investigation; cellular; mechanism; PQBP1; dependant

In a collaborative publication, we identified PQBP1 as an essential component of the cGAS/IRF3-dependent innate response to HIV. We could demonstrate that PQBP1 binds directly to HIV-1 reverse-transcribed DNA intermediates, and binds to cGAS to induce STING/IRF3 signaling. Interestingly, the requirement for PQBP1 appears to be specific for lentiviral DNA, as other types of DNA, including poxvirus, did not require PQBP1 to stimulate innate immune responses. The main goals of this project are to define the specificity of PQBP1-dependent sensing and the underlying mechanisms. Initially, we will examine other genera of the Retroviridae family in comparison to DNA viruses to understand the breadth of PQBP1 recognition. Moreover, we aim to detect the reverse transcribed DNA intermediates bound to PQBP1 in order to understand their commonalities. Furthermore, we aim to analyze whether cGAS is required for this step. Furthermore, we are interested in the underlying mechanisms. We will determine whether infection of viruses recognized by PQBP1 specifically enhance the binding between PQBP1 and cGAS and whether specific PTMs are involved. Our results will provide new insights into the cellular mechanism underlying PQBP1-dependant innate signaling of HIV-1.

在一份合作出版物中，我们确定 PQBP1 是 cGAS/IRF3 依赖性 HIV 先天反应的重要组成部分。我们可以证明 PQBP1 直接与 HIV-1 逆转录 DNA 中间体结合，并与 cGAS 结合以诱导 STING/IRF3 信号传导。 有趣的是，对 PQBP1 的需求似乎是慢病毒 DNA 所特有的，因为包括痘病毒在内的其他类型的 DNA 不需要 PQBP1 来刺激先天免疫反应。该项目的主要目标是定义 PQBP1 依赖性传感的特异性和潜在机制。首先，我们将检查逆转录病毒科的其他属与 DNA 病毒进行比较，以了解 PQBP1 识别的广度。此外，我们的目标是检测与 PQBP1 结合的逆转录 DNA 中间体，以了解它们的共性。此外，我们的目的是分析此步骤是否需要 cGAS。此外，我们对底层机制感兴趣。我们将确定PQBP1识别的病毒感染是否特异性增强PQBP1和cGAS之间的结合以及是否涉及特定的PTM。我们的结果将为 HIV-1 依赖 PQBP1 的先天信号传导的细胞机制提供新的见解。