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Review
. 2017 Oct 21;9(10):308.
doi: 10.3390/v9100308.

Gammaherpesviral Tegument Proteins, PML-Nuclear Bodies and the Ubiquitin-Proteasome System

Florian Full  1 , Alexander S Hahn  2 , Anna K Großkopf  3 , Armin Ensser  4
Affiliations
Review

Gammaherpesviral Tegument Proteins, PML-Nuclear Bodies and the Ubiquitin-Proteasome System

Florian Full et al. Viruses. .

Abstract

Gammaherpesviruses like Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) subvert the ubiquitin proteasome system for their own benefit in order to facilitate viral gene expression and replication. In particular, viral tegument proteins that share sequence homology to the formylglycineamide ribonucleotide amidotransferase (FGARAT, or PFAS), an enzyme in the cellular purine biosynthesis, are important for disrupting the intrinsic antiviral response associated with Promyelocytic Leukemia (PML) protein-associated nuclear bodies (PML-NBs) by proteasome-dependent and independent mechanisms. In addition, all herpesviruses encode for a potent ubiquitin protease that can efficiently remove ubiquitin chains from proteins and thereby interfere with several different cellular pathways. In this review, we discuss mechanisms and functional consequences of virus-induced ubiquitination and deubiquitination for early events in gammaherpesviral infection.

Keywords: EBV; Epstein-Barr virus; Gammaherpesvirus; KSHV; Kaposi’s sarcoma-associated herpesvirus; PML nuclear bodies; deubiquitinating enzyme; proteasome; ubiquitin; viral FGARAT.

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Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the writing of the manuscript, and in the decision to publish the manuscript.

Figures

Figure 1
Figure 1
Modulation of the host ubiquitin-proteasome system and the innate immune response by gamma-herpesviral effector proteins. Gamma-herpesviral ORF64 homologs act as viral ubiquitin proteases interfering with different cellular pathways (grey boxes) resulting for example in a decreased Type I interferon response and pro-inflammatory cytokine production (left). Viral proteins, including the viral formylglycineamide ribonucleotide amidotransferase (FGARAT) homologs (light blue) disrupt the intrinsic antiviral response associated with PML-NBs by targeting different PML-NB components (right) through proteosomal and non-proteosomal/ unknown modes of action (grey box). Abbreviations: Ub, ubiquitin; S, SUMOylation; P, phosphorylation; StUbL, SUMO-targeted ubiquitin ligase; RR1, large subunit of EBV ribonucleotide reductase; RR2, small subunit of EBV ribonucleotide reductase; LMP-1, latent membrane protein 1. The Herpes simplex ICP0 and human Cytomegalovirus IE1 proteins were included for reference. Red bar-headed lines indicate removal of post-translational modifications, black bar-headed lines indicate inhibition, ? indicates unknown mechanisms; arrow-headed lines indicate interaction; solid lines indicate direct interaction, dotted lines indirect interaction; the yellow area represent PML-NB-associated functions.
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