In vivo relevance of the Schlafen-mediated innate immune mechanism in flavivirus infection

摘要 黄病毒是重要的人类病原体，包括西尼罗河病毒、登革热病毒和寨卡病毒。不是 针对这些感染有特定的治疗方法或疫苗可用，而且没有生物标记物可以 预测他们的结果，以重要的临床变异性为特征。了解先天抗病毒免疫 对黄病毒的反应，可能导致识别疾病易感性生物标志物和 治疗靶点。我们最近证明了I型干扰素刺激蛋白Schlafen 11 (SLFN11)是一种新的有效的黄病毒限制因子。在本申请中，我们的目标是在分子上定义 水平，SLFN11作用机制的几个方面，并确定其他化合物的抗黄病毒活性 SLFN家族的成员以及这一防御系统的体内相关性。因此，这 研究具有很高的相关性，并将极大地促进我们对抗病毒机制的理解 SLFN蛋白的作用，目前尚不清楚。

ABSTRACT Flaviviruses are important human pathogens including viruses such as West Nile, dengue, and Zika. No specific treatments or vaccines are available against these infections, and no biomarkers exist that allow predicting their outcome, characterized by important clinical variability. Understanding innate antiviral immune responses against flaviviruses, could lead to the identification of disease susceptibility biomarkers and therapeutic targets. We recently demonstrated that the type I interferon-stimulated protein Schlafen 11 (SLFN11) is a novel and potent flavivirus restriction factor. In this application we aim to define, at the molecular level, several aspects of the mechanism of action of SLFN11 and determine the anti-flavivirus activity of other members of the SLFN family, as well as the in vivo relevance of this defense system. Therefore, this investigation is highly relevant and will significantly advance our understanding of the antiviral mechanism of action of SLFN proteins, which is currently unknown.