The role of autophagy during viral infection

自噬是一种进化上高度保守和复杂调控的降解途径。重要的是，它代表了一种强大的细胞内在抗病毒防御机制，病毒感染通常会诱导自噬。在自噬过程中，细胞质货物被双膜小泡吞噬，这些小泡最终在与溶酶体融合时被降解。货物可以是由专用受体识别的病毒或病毒组件，并直接作为销毁的目标。此外，通过将病原体相关的分子模式暴露于免疫受体，自噬可能有助于识别病毒。此外，在自噬过程中由病毒成分产生的多肽作为病毒抗原呈递给免疫细胞。然而，病毒已经进化出逃避自噬或利用它来促进复制的策略。虽然自噬的基本原理已经有了很好的描述，但关于感染引发的自噬以及自噬和病毒之间的相互作用，人们知之甚少。本项目旨在研究病毒诱导的自噬过程中关键蛋白的作用及其对病毒病原体的影响。我们的初步数据证实，甲型流感病毒(IAV)诱导自噬所需的三方基序蛋白4(TRIM4)和TRIM20是必需的，但不是单纯疱疹病毒1(HSV-1)。我们打算探索TRIM介导的自噬的病毒特异性的分子机制(S)，并研究TRIM依赖的自噬、病毒和其他抗病毒防御途径之间的相互作用。我们的初步数据进一步表明，与TRIM23相关的ADP核糖化因子(ARF)蛋白参与了自噬。利用人类两种重要的病原体，人类免疫缺陷病毒-1(HIV-1)和IAV，我们旨在研究ARF依赖病毒诱导的自噬的影响和调控。最后，我们打算探索ARF蛋白介导自噬诱导的分子机制(S)。综上所述，研究病毒诱导的自噬可能有助于为基于自噬的新型抗病毒疗法铺平道路。此外，我们还将对介导病毒诱导的自噬的关键因素以及病毒和人类防御机制之间复杂的相互作用获得基本的见解。

Autophagy is an evolutionary highly conserved and intricately regulated degradation pathway. Importantly, it represents a powerful cell-intrinsic anti-viral defense mechanism and viral infections typically induce autophagy. During autophagy, cytoplasmic cargoes are engulfed by double-membrane vesicles, which are eventually degraded upon fusion with lysosomes. Cargoes can be viruses or viral components that are recognized by dedicated receptors and directly targeted for destruction. Additionally, by exposing pathogen-associated molecular patterns to immune receptors autophagy may facilitate recognition of viruses. Moreover, peptides generated from viral components during autophagy are presented to immune cells as viral antigens. However, viruses have evolved strategies to evade autophagy or exploit it to facilitate their replication. While the basic principles of autophagy are well-characterized, there is little known about infection-triggered autophagy and the interplay between autophagy and viruses. This project aims to characterize the role of key proteins during virus-induced autophagy and their impact on viral pathogens. Our preliminary data identified Tripartide Motif protein 4 (TRIM4) and TRIM20 as required for autophagy induced by influenza A virus (IAV), but not Herpes-simplex virus 1 (HSV-1). We intend to explore the molecular mechanism(s) underlying the virus specificity of TRIM-mediated autophagy and study the TRIM-dependent interplay between autophagy, viruses and other anti-viral defense pathways. Our preliminary data further indicates that TRIM23-related ADP-ribosylation factor (ARF) proteins are involved in autophagy. Using two important human pathogens, human immunodeficiency virus-1 (HIV-1) and IAV, we aim to study the impact and regulation of ARF-dependent virus-induced autophagy. Finally, we intend to explore the molecular mechanism(s) how ARF proteins mediate autophagy induction. Taken together, studying virus-induced autophagy may help to pave the way for novel anti-viral therapies based on autophagy. Furthermore, we will gain fundamental insights on key factors mediating virus-induced autophagy and the intricate interplay between viruses and human defense mechanisms.