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Interplay between viruses and host sumoylation pathways

Nature Reviews Microbiology volume 11, pages 400–411 (2013)Cite this article

Subjects

Key Points

  • Small ubiquitin-like modifier (SUMO) proteins are structurally closely related to ubiquitin and can be covalently conjugated to other proteins to regulate their activity, intracellular localization or interaction partners.

  • Many viral proteins can be sumoylated, can influence the sumoylation of cellular proteins or can engage with regulatory pathways that have SUMO-dependent control points.

  • Promyelocytic leukaemia nuclear bodies in uninfected cell nuclei are major hubs of sumoylation and have significant antiviral roles. Several viruses disrupt the antiviral functions of these nuclear bodies through SUMO-related mechanisms.

  • There are emerging roles for SUMO pathways in intrinsic and innate immune defences against viral infection.

Abstract

Post-translational modification by members of the small ubiquitin-like modifier (SUMO) family of proteins is important for the regulation of many cellular proteins and pathways. As obligate parasites, viruses must engage with the host cell throughout their replication cycles, and it is therefore unsurprising that there are many examples of interplay between viral proteins and the host sumoylation system. This article reviews recent advances in this field, summarizing information on sumoylated viral proteins, the varied ways in which viruses engage with SUMO-related pathways, and the consequences of these interactions for viral replication and engagement with innate and intrinsic immunity.

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Figure 1: The sumoylation pathway.
Figure 2: Functional consequences of sumoylation.
Figure 3: Effects of viral proteins on PML nuclear bodies via sumoylation or sumoylated proteins.
Figure 4: Overview of viral protein engagement with sumoylation events.

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Acknowledgements

Work in the R.D.E. and C.B. laboratories is funded by the UK Medical Research Council. B.G.H. acknowledges funding support from the UK Medical Research Council, the University of Glasgow, UK, and the European Commission (Framework Programme 7 Marie Curie career integration grant 321703 as part of project UBIFLU).

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  1. MRC-University of Glasgow Centre for Virus Research, 8 Church Street, Glasgow, G11 5JR, UK

    Roger D. Everett, Chris Boutell & Benjamin G. Hale

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  1. Roger D. Everett
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Correspondence to Roger D. Everett.

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Supplementary information

Supplementary Table 1

Summary of identified SUMO modified viral proteins (PDF 317 kb)

Supplementary Table 2

Interactions of viral proteins with components of the SUMO modification pathway (PDF 314 kb)

Glossary

Small ubiquitin-like modifier

(SUMO). A family of small proteins that are related to ubiquitin and that can be conjugated to substrate proteins through isopeptide linkages.

Protein inhibitor of activated STAT

(PIAS). A family of small ubiquitin-like modifier (SUMO) E3 ligases with RING-related catalytic domains.

SUMO-targeted ubiquitin ligases

(STUbLs). A class of ubiquitin E3 ligases that interact with small ubiquitin-like modifier (SUMO) and ubiquitylate sumoylated proteins.

STAT

(Signal transducer and activator of transcription). A family of proteins that engage in both interferon-regulated signal transduction in the cytoplasm and, after phosphorylation and nuclear translocation, the assembly of transcriptional activation complexes on the promoters of interferon-stimulated genes.

Interferon

(IFN). A family of small proteins that are synthesized in response to pathogens and which initiate signal transduction pathways in infected and surrounding cells to induce innate immune responses.

RING finger

A protein motif in which two zinc atoms are coordinated by Cys and His residues in a cross-braced fold that frequently confers ubiquitin or small ubiquitin-like modifier (SUMO) E3 ligase activity.

Pattern recognition receptors

(PRRs). Proteins that recognize pathogen-associated molecular signals in the initial stages of innate immune responses.

Interferon-regulatory factor

(IRF). A family of proteins that are components of transcription complexes which regulate the transcription of interferon-responsive genes.

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Everett, R., Boutell, C. & Hale, B. Interplay between viruses and host sumoylation pathways. Nat Rev Microbiol 11, 400–411 (2013). https://doi.org/10.1038/nrmicro3015

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