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Quantitative Temporal Proteomic Analysis of Vaccinia Virus Infection Reveals Regulation of Histone Deacetylases by an Interferon Antagonist.

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Albarnaz, Jonas D 
Davies, Colin TR 
Antrobus, Robin 


Vaccinia virus (VACV) has numerous immune evasion strategies, including multiple mechanisms of inhibition of interferon regulatory factor 3 (IRF-3), nuclear factor κB (NF-κB), and type I interferon (IFN) signaling. Here, we use highly multiplexed proteomics to quantify ∼9,000 cellular proteins and ∼80% of viral proteins at seven time points throughout VACV infection. A total of 265 cellular proteins are downregulated >2-fold by VACV, including putative natural killer cell ligands and IFN-stimulated genes. Two-thirds of these viral targets, including class II histone deacetylase 5 (HDAC5), are degraded proteolytically during infection. In follow-up analysis, we demonstrate that HDAC5 restricts replication of both VACV and herpes simplex virus type 1. By generating a protein-based temporal classification of VACV gene expression, we identify protein C6, a multifunctional IFN antagonist, as being necessary and sufficient for proteasomal degradation of HDAC5. Our approach thus identifies both a host antiviral factor and a viral mechanism of innate immune evasion.



histone deacetylase, host-pathogen interaction, immune evasion, innate immunity, interferon, poxvirus, quantitative proteomics, restriction factor, systems virology, tandem mass tag, Cytomegalovirus, Down-Regulation, Gene Expression Regulation, Viral, Herpesvirus 1, Human, Histone Deacetylases, Host-Pathogen Interactions, Humans, Immune Evasion, Interferons, Membrane Proteins, Proteasome Endopeptidase Complex, Proteolysis, Proteomics, Time Factors, Vaccinia, Vaccinia virus, Viral Proteins

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Cell Rep

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Elsevier BV


All rights reserved
Wellcome Trust (108070/Z/15/Z)
Wellcome Trust (090315/Z/09/Z)
Wellcome Trust (090315/B/09/A)
Wellcome Trust (100140/Z/12/Z)
Cambridge Biomedical Research Centre, UK