ISG15 in antiviral immunity and beyond

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

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.

Abstract

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.

Related collections

Most cited references 112

Record: found
Abstract: found
Article: not found

Systematic and quantitative assessment of the ubiquitin-modified proteome.

Woong Kim, Eric J. Bennett, Edward L. Huttlin … (2011)

Despite the diverse biological pathways known to be regulated by ubiquitylation, global identification of substrates that are targeted for ubiquitylation has remained a challenge. To globally characterize the human ubiquitin-modified proteome (ubiquitinome), we utilized a monoclonal antibody that recognizes diglycine (diGly)-containing isopeptides following trypsin digestion. We identify ~19,000 diGly-modified lysine residues within ~5000 proteins. Using quantitative proteomics we monitored temporal changes in diGly site abundance in response to both proteasomal and translational inhibition, indicating both a dependence on ongoing translation to observe alterations in site abundance and distinct dynamics of individual modified lysines in response to proteasome inhibition. Further, we demonstrate that quantitative diGly proteomics can be utilized to identify substrates for cullin-RING ubiquitin ligases. Interrogation of the ubiquitinome allows for not only a quantitative assessment of alterations in protein homeostasis fidelity, but also identification of substrates for individual ubiquitin pathway enzymes. Copyright © 2011 Elsevier Inc. All rights reserved.

0 comments Cited 612 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays.

S. Der, A. Zhou, B R Williams … (1998)

The pleiotropic activities of interferons (IFNs) are mediated primarily through the transcriptional regulation of many downstream effector genes. The mRNA profiles from IFN-alpha, -beta, or -gamma treatments of the human fibrosarcoma cell line, HT1080, were determined by using oligonucleotide arrays with probe sets corresponding to more than 6,800 human genes. Among these were transcripts for known IFN-stimulated genes (ISGs), the expression of which were consistent with previous studies in which the particular ISG was characterized as responsive to either Type I (alpha, beta) or Type II (gamma) IFNs, or both. Importantly, many novel IFN-stimulated genes were identified that were diverse in their known biological functions. For instance, several novel ISGs were identified that are implicated in apoptosis (including RAP46/Bag-1, phospholipid scramblase, and hypoxia inducible factor-1alpha). Furthermore, several IFN-repressed genes also were identified. These results demonstrate the usefulness of oligonucleotide arrays in monitoring mammalian gene expression on a broad and unprecedented scale. In particular, these findings provide insights into the basic mechanisms of IFN actions and ultimately may contribute to better therapeutic uses for IFNs.

0 comments Cited 320 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I.

Rhea Sumpter, Yueh-Ming Loo, Eileen Foy … (2005)

Virus-responsive signaling pathways that induce alpha/beta interferon production and engage intracellular immune defenses influence the outcome of many viral infections. The processes that trigger these defenses and their effect upon host permissiveness for specific viral pathogens are not well understood. We show that structured hepatitis C virus (HCV) genomic RNA activates interferon regulatory factor 3 (IRF3), thereby inducing interferon in cultured cells. This response is absent in cells selected for permissiveness for HCV RNA replication. Studies including genetic complementation revealed that permissiveness is due to mutational inactivation of RIG-I, an interferon-inducible cellular DExD/H box RNA helicase. Its helicase domain binds HCV RNA and transduces the activation signal for IRF3 by its caspase recruiting domain homolog. RIG-I is thus a pathogen receptor that regulates cellular permissiveness to HCV replication and, as an interferon-responsive gene, may play a key role in interferon-based therapies for the treatment of HCV infection.

0 comments Cited 237 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Deborah J. Lenschow: dlenschow@wustl.edu

Journal

Journal ID (nlm-ta): Nat Rev Microbiol

Journal ID (iso-abbrev): Nat. Rev. Microbiol

Title: Nature Reviews. Microbiology

Publisher: Nature Publishing Group UK (London )

ISSN (Print): 1740-1526

ISSN (Electronic): 1740-1534

Publication date (Electronic): 16 May 2018

Publication date (Print): 2018

Volume: 16

Issue: 7

Pages: 423-439

Affiliations

[1 ]ISNI 0000 0001 2355 7002, GRID grid.4367.6, Department of Internal Medicine, , Washington University School of Medicine, ; St Louis, MO USA

[2 ]ISNI 0000 0001 2355 7002, GRID grid.4367.6, Department of Pathology and Immunology, , Washington University School of Medicine, ; St Louis, MO USA

Article

Publisher ID: 20

DOI: 10.1038/s41579-018-0020-5

PMC ID: 7097117

PubMed ID: 29769653

SO-VID: 72d4b370-8766-438e-a7da-8631bd4fb98a

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.