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，我们将PQBP 1确定为cGAS/IRF 3依赖性先天性HIV应答的重要组成部分。我们可以证明PQBP 1直接与HIV-1逆转录的DNA中间体结合，并与cGAS结合以诱导STING/IRF 3信号传导。 有趣的是，对PQBP 1的需求似乎对慢病毒DNA是特异性的，因为其他类型的DNA，包括痘病毒，不需要PQBP 1来刺激先天免疫应答。该项目的主要目标是确定PQBP 1依赖性传感的特异性和潜在的机制。首先，我们将研究逆转录病毒科的其他属与DNA病毒的比较，以了解PQBP 1识别的广度。此外，我们的目标是检测与PQBP 1结合的逆转录DNA中间体，以了解它们的共性。此外，我们的目标是分析这一步骤是否需要cGAS。此外，我们对潜在的机制感兴趣。我们将确定PQBP 1识别的病毒感染是否特异性增强PQBP 1和cGAS之间的结合，以及是否涉及特异性PTM。我们的研究结果将为HIV-1依赖PQBP 1的先天信号转导的细胞机制提供新的见解。