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

干扰素系统是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干扰素的表达。随后，干扰素与未感染细胞的结合诱导了几个编码具有抗病毒活性的蛋白质的基因的表达。结果，细胞转变为抗病毒状态。最近的一项研究表明，干扰素诱导无转运蛋白(SFL)的表达，通过抑制必要的病毒多蛋白Gag-Pol的表达所需的-1程序性核糖体移码事件(-1PRF)来抑制人类免疫缺陷病毒(HIV)的感染。然而，目前尚不清楚SFL是如何抑制-1PRF的，以及抑制在多大程度上有助于阻断干扰素对HIV的感染。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在干扰素介导的抑制HIV感染中的作用。我们将使用体外翻译系统和突变分析来揭示SFL是如何干扰-1PRF的。最后，将确定SFL、病毒RNA和核糖体的复合体的结构。总之，将分析SFL在艾滋病毒感染中的作用，总体目标是了解先天免疫如何抑制逆转录病毒感染。

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.