ISG15 in antiviral immunity and beyond

• Published in: Nature reviews. Microbiology Vol. 16; no. 7; pp. 423 - 439
• Main Authors: Perng, Yi-Chieh, Lenschow, Deborah J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2018; Nature Publishing Group
• Subjects: 13; 13/1; 631/250/255/2514; 631/326/596/2553; 631/326/596/2557; 82/58; Antiviral agents; Antiviral drugs; Biological response modifiers; Biomedical and Life Sciences; Care and treatment; Cell receptors; Cellular proteins; Cytokines - immunology; Cytokines - metabolism; Development and progression; Genes; Genetic aspects; Health aspects; Host-virus relationships; Humans; Immune response; Immune system; Immunity; Infection; Infections; Infectious Diseases; Interferon; Life Sciences; Medical Microbiology; Microbiology; Parasitology; Proteins; Review; Review Article; Signal transduction; Ubiquitin; Ubiquitins - immunology; Ubiquitins - metabolism; Viral infections; Virology; Virus diseases; Virus Diseases - immunology; Virus Physiological Phenomena; Virus replication; Viruses - immunology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/s41579-018-0020-5

The host response to viral infection includes the induction of type I interferons and the subsequent upregulation of hundreds of interferon-stimulated genes. Ubiquitin-like protein ISG15 is an interferon-induced protein that has been implicated as a central player in the host antiviral response. Over the past 15 years, efforts to understand how ISG15 protects the host during infection have revealed that its actions are diverse and pathogen-dependent. In this Review, we describe new insights into how ISG15 directly inhibits viral replication and discuss the recent finding that ISG15 modulates the host damage and repair response, immune response and other host signalling pathways. We also explore the viral immune-evasion strategies that counteract the actions of ISG15. These findings are integrated with a discussion of the recent identification of ISG15-deficient individuals and a cellular receptor for ISG15 that provides new insights into how ISG15 shapes the host response to viral infection. Ubiquitin-like protein ISG15 is an interferon-induced protein that has been implicated as a central player in the host antiviral response. In this Review, Perng and Lenschow provide new insights into how ISG15 restricts and shapes the host response to viral infection and the viral immune-evasion strategies that counteract ISG15.