The innate immune system offers a first line of defense by neutralizing foreign pathogens such as bacteria, fungi, and viruses. These pathogens express molecules (RNA and proteins) that have discrete structures, known as the pathogen-associated molecular patterns that are recognized by a highly specialized class of host proteins called pattern recognition receptors to facilitate the host’s immune response against infection. The RNA-dependent Protein Kinase R (PKR) is one of the host’s pattern recognition receptors that is a key component of an innate immune system. PKR recognizes imperfectly double-stranded non-coding viral RNA molecules via its N-terminal double-stranded RNA binding motifs, undergoes phosphorylation of the C-terminal kinase domain, ultimately resulting in inhibition of viral protein translation by inhibiting the guanine nucleotide exchange activity of eukaryotic initiation factor 2α. Not surprisingly, viruses have evolved mechanisms by which viral non-coding RNA or protein molecules inhibit PKR’s activation and/or its downstream activity to allow viral replication. In this review, we will highlight the role of viral proteins in inhibiting PKR’s activity and summarize currently known mechanisms by which viral proteins execute such inhibitory activity.

先天免疫系统通过中和外来病原体，例如细菌，真菌和病毒，提供了第一道防线。这些病原体表达具有离散结构的分子（RNA和蛋白质），称为病原体相关分子模式，可被称为模式识别受体的高度专业化的宿主蛋白识别，以促进宿主对感染的免疫反应。RNA依赖性蛋白激酶R（PKR）是宿主的模式识别受体之一，是先天免疫系统的关键组成部分。PKR通过其N端双链RNA结合基序识别不完美的双链非编码病毒RNA分子，并经过C端激酶结构域的磷酸化，通过抑制真核起始因子2α的鸟嘌呤核苷酸交换活性，最终导致病毒蛋白翻译受到抑制。毫不奇怪，病毒已经进化出机制，病毒非编码RNA或蛋白质分子可通过这种机制抑制PKR的激活和/或其下游活性，从而实现病毒复制。在这篇综述中，我们将重点介绍病毒蛋白在抑制PKR活性中的作用，并概述病毒蛋白执行这种抑制活性的当前已知机制。