Interferon-induced ISG15 pathway: an ongoing virus-host battle - PubMed (original) (raw)

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Interferon-induced ISG15 pathway: an ongoing virus-host battle

Chen Zhao et al. Trends Microbiol. 2013 Apr.

Abstract

ISG15 is an interferon (IFN)-induced ubiquitin-like protein that is conjugated to target proteins via the sequential action of three enzymes that are also induced by IFN. Unlike ubiquitin, which is highly conserved, the sequence of ISG15 varies between species. ISG15 conjugation inhibits many viruses, and free (unconjugated) ISG15 can also act as an antiviral protein. In this review, we focus on the antiviral role of ISG15 conjugation and on countermeasures employed by several viruses. The countermeasure by influenza B virus is unique in that it exhibits species specificity. Only the antiviral activity of human and non-human primate ISG15s can be blocked, providing one possible explanation for the restriction of influenza B virus to humans.

Copyright © 2013 Elsevier Ltd. All rights reserved.

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Figures

Figure 1

Figure 1

Two viral proteins that bind ISG15. (a) Influenza NS1B–N-terminal domain region (NTR) homodimer (green and cyan chains) binds two human ISG15 molecules (magenta) via their N-terminal ubiquitin-like (Ubl) domains. Generated from the Protein Data Bank (PDB) ID: 3SDL. (b) The deconjugating viral ovarian tumor (OTU) domain of Crimean Congo hemorrhagic fever virus (CCHFV; green) bound to human ISG15 substrate (magenta). The viral OTU binds the C-terminal Ubl domain of ISG15 with the C-terminus trapped as covalent intermediate. Generated from PDB ID:

3PSE

. The missing loop in the ISG15 N-terminal Ubl is shown with a dashed line.

Figure 2

Figure 2

Alignment of ISG15 sequences from four species: human, rhesus monkey, mouse, and dog. Generated from National Center for Biotechnology Information (NCBI) accession numbers: NP_005092, NP_001253735, NP_056598, and XP_003639101, respectively). The five-amino acid hinge between the N-terminal and C-terminal ubiquitin-like (Ubl) domains is enclosed in a red box. Dark blue shading denotes amino acids that are conserved in all four ISG15 molecules; lighter blue shading denotes amino acids that are present in three or two of the ISG15 molecules.

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