Department of Microbiology and Immunology, University of Illinois at Chicago, College of Medicine, Chicago, IL, United States.
Front Immunol. 2022 Oct 24;13:1035559. doi: 10.3389/fimmu.2022.1035559. eCollection 2022.
SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 encodes nine accessory proteins that are involved in host-pathogen interaction. ORF8 is unique among these accessory proteins. SARS-CoV-2 ORF8 shares a surprisingly low amino acid sequence similarity with SARS-COV ORF8 (30%), and it is presumed to have originated from bat. Studies have shown that ORF8 exerts multiple different functions that interfere with host immune responses, including the downregulation of MHC class I molecules. These functions may represent strategies of host immune evasion. The x-ray crystal structure of ORF8 revealed an immunoglobulin-like domain with several distinguishing features. To date, there are numerous unanswered questions about SARS-CoV-2 ORF8 protein and its structure-function relationship that we discuss in this mini-review. A better understanding of how ORF8 interacts with components of the immune system is needed for elucidating COVID-19 pathogenesis and to develop new avenues for the treatment of the disease.
SARS-CoV-2 是导致 COVID-19 大流行的病毒。SARS-CoV-2 的基因组编码了 9 种辅助蛋白，这些蛋白参与宿主-病原体相互作用。ORF8 是这些辅助蛋白中独特的一种。SARS-CoV-2 的 ORF8 与 SARS-CoV 的 ORF8 （30%）的氨基酸序列相似度惊人地低，据推测它起源于蝙蝠。研究表明，ORF8 发挥了多种不同的功能，干扰了宿主的免疫反应，包括 MHC Ⅰ类分子的下调。这些功能可能代表了宿主免疫逃避的策略。ORF8 的 X 射线晶体结构揭示了一个具有几个独特特征的免疫球蛋白样结构域。迄今为止，关于 SARS-CoV-2 ORF8 蛋白及其结构-功能关系仍有许多悬而未决的问题，我们在这篇综述中进行了讨论。为了阐明 COVID-19 的发病机制，并为该疾病的治疗开辟新途径，我们需要更好地了解 ORF8 如何与免疫系统的成分相互作用。
