Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
Center for Predictive Medicine for Biodefense and Emerging Infectious Disease (CPM), University of Louisville, Louisville, KY 40202, USA.
Viruses. 2023 Jan 5;15(1):164. doi: 10.3390/v15010164.
Alphaviruses are arthropod-borne, single-stranded positive sense RNA viruses that rely on the engagement of host RNA-binding proteins to efficiently complete the viral lifecycle. Because of this reliance on host proteins, the identification of host/pathogen interactions and the subsequent characterization of their importance to viral infection has been an intensive area of study for several decades. Many of these host protein interaction studies have evaluated the Protein:Protein interactions of viral proteins during infection and a significant number of host proteins identified by these discovery efforts have been RNA Binding Proteins (RBPs). Considering this recognition, the field has shifted towards discovery efforts involving the direct identification of host factors that engage viral RNAs during infection using innovative discovery approaches. Collectively, these efforts have led to significant advancements in the understanding of alphaviral molecular biology; however, the precise extent and means by which many RBPs influence viral infection is unclear as their specific contributions to infection, as per any RNA:Protein interaction, have often been overlooked. The purpose of this review is to summarize the discovery of host/pathogen interactions during alphaviral infection with a specific emphasis on RBPs, to use new ontological analyses to reveal potential functional commonalities across alphaviral RBP interactants, and to identify host RBPs that have, and have yet to be, evaluated in their native context as RNA:Protein interactors.
甲病毒是节肢动物传播的单链正链 RNA 病毒,依赖于宿主 RNA 结合蛋白的参与来有效地完成病毒生命周期。由于这种对宿主蛋白的依赖,宿主/病原体相互作用的鉴定及其对病毒感染的重要性的后续特征已成为数十年来的一个密集研究领域。这些宿主蛋白相互作用研究中的许多都评估了病毒蛋白在感染过程中的蛋白:蛋白相互作用,并且通过这些发现工作鉴定的许多宿主蛋白都是 RNA 结合蛋白(RBPs)。考虑到这一认识,该领域已转向利用创新的发现方法直接鉴定感染过程中与病毒 RNA 结合的宿主因子的发现工作。总的来说,这些努力极大地促进了对甲病毒分子生物学的理解;然而,许多 RBPs 影响病毒感染的确切程度和方式尚不清楚,因为它们对感染的具体贡献(就任何 RNA:蛋白相互作用而言)经常被忽视。本文综述了甲病毒感染过程中宿主/病原体相互作用的发现,特别强调了 RBPs,利用新的本体论分析揭示了甲病毒 RBP 相互作用体之间的潜在功能共性,并确定了已在其天然环境中作为 RNA:蛋白相互作用体进行评估和尚未进行评估的宿主 RBPs。