HERC5 和 ISGylation 途径：抗病毒免疫反应的关键调节因子。
HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response.
机构信息
Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, 950 Main St., Worcester, MA 01610, USA.
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, 1151 Richmond St., London, ON N6A 5C1, Canada.
出版信息
Viruses. 2021 Jun 9;13(6):1102. doi: 10.3390/v13061102.
Mammalian cells have developed an elaborate network of immunoproteins that serve to identify and combat viral pathogens. Interferon-stimulated gene 15 (ISG15) is a 15.2 kDa tandem ubiquitin-like protein (UBL) that is used by specific E1-E2-E3 ubiquitin cascade enzymes to interfere with the activity of viral proteins. Recent biochemical studies have demonstrated how the E3 ligase HECT and RCC1-containing protein 5 (HERC5) regulates ISG15 signaling in response to hepatitis C (HCV), influenza-A (IAV), human immunodeficiency virus (HIV), SARS-CoV-2 and other viral infections. Taken together, the potent antiviral activity displayed by HERC5 and ISG15 make them promising drug targets for the development of novel antiviral therapeutics that can augment the host antiviral response. In this review, we examine the emerging role of ISG15 in antiviral immunity with a particular focus on how HERC5 orchestrates the specific and timely ISGylation of viral proteins in response to infection.
哺乳动物细胞已经进化出了一套复杂的免疫蛋白网络，用于识别和对抗病毒病原体。干扰素刺激基因 15（ISG15）是一种 15.2 kDa 的串联泛素样蛋白（UBL），它被特定的 E1-E2-E3 泛素级联酶用于干扰病毒蛋白的活性。最近的生化研究表明，HECT 和包含 RCC1 的蛋白 5（HERC5）E3 连接酶如何调节 ISG15 信号转导，以响应丙型肝炎（HCV）、甲型流感（IAV）、人类免疫缺陷病毒（HIV）、SARS-CoV-2 和其他病毒感染。总之，HERC5 和 ISG15 表现出的强大抗病毒活性使它们成为开发新型抗病毒治疗药物的有前途的靶点，这些药物可以增强宿主的抗病毒反应。在这篇综述中，我们研究了 ISG15 在抗病毒免疫中的新作用，特别关注 HERC5 如何在感染时协调病毒蛋白的特异性和适时的 ISG 化。
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