Role of Shiftless in HIV infection: Antiviral mechanism and contribution to innate immune responses

Shiftless 在 HIV 感染中的作用：抗病毒机制及其对先天免疫反应的贡献

• 批准号: 429513786
• 负责人: Professor Dr. Stefan Pöhlmann
• 金额: --
• 依托单位: Abteilung Infektionsbiologie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/429513786?language=en
• 关键词: Role; Shiftless; HIV; infection; Antiviral

The interferon (IFN) system constitutes the first line of defense against viral infection. Sensors of the IFN system recognize invading viruses and induce the expression of IFN. Subsequently, the binding of IFN to uninfected cells induces the expression of several genes encoding for proteins with antiviral activity. As a consequence, the cell transits into an antiviral state. A recent study shows that IFN induces the expression of the Shiftless (SFL) protein, which inhibits human immunodeficiency virus (HIV) infection by suppressing a –1 programmed ribosomal frameshifting event (–1PRF) required for expression of the essential viral polyprotein Gag-Pol. However, it is currently unclear how SFL inhibits –1PRF and to what extend inhibition contributes to blockade of HIV infection by IFN. In this project, we will clarify which viral target cells express SFL and elucidate the contribution of SFL to IFN-mediated inhibition of HIV infection. We will employ in vitro translation systems and mutagenic analysis to reveal how SFL interferes with –1PRF. Finally, the structure of the complex of SFL, viral RNA und ribosome will be determined. Collectively, the role of SFL in HIV infection will be analyzed with the overall goal of understanding how innate immunity can inhibit retroviral infection.

干扰素 (IFN) 系统构成抵御病毒感染的第一道防线，干扰素系统的传感器识别入侵的病毒并诱导 IFN 的表达，随后 IFN 与未感染细胞的结合诱导编码蛋白质的多种基因的表达。因此，细胞会转变为抗病毒状态，IFN 会诱导 Shiftless (SFL) 蛋白的表达，从而抑制人类免疫缺陷病毒。 (HIV) 感染通过抑制必需病毒多蛋白 Gag-Pol 表达所需的 –1 程序性核糖体移码事件 (–1PRF) 然而，目前尚不清楚 SFL 如何抑制 –1PRF 以及抑制作用在多大程度上有助于阻断​​ HIV。在这个项目中，我们将阐明哪些病毒靶细胞表达 SFL，并阐明 SFL 对 IFN 介导的 HIV 感染抑制的作用。我们将采用体外翻译系统和诱变。分析揭示 SFL 如何干扰 –1PRF。最后，将确定 SFL、病毒 RNA 和核糖体复合物的结构，总体目标是了解先天免疫如何发挥作用。抑制逆转录病毒感染。