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

在一份合作出版物中，我们发现PQBP1是依赖cGAS/IRF3的艾滋病毒先天反应的重要组成部分。我们可以证明PQBP1直接与HIV-1反转录的DNA中间体结合，并与cGAS结合以诱导STIN/IRF3信号转导。有趣的是，对PQBP1的要求似乎是慢病毒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来刺激先天性免疫反应。这个项目的主要目标是确定依赖PQBP1的感觉的特异性和潜在的机制。首先，我们将检查逆转录病毒科的其他属与DNA病毒的比较，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PQBP1识别的病毒感染是否特异性地增强PQBP1与cGAS之间的结合，以及是否涉及特定的PTM。我们的结果将为PQBP1依赖的HIV-1先天信号背后的细胞机制提供新的见解。

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.