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Publication

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

Cell reports | 2019

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.

Pubmed ID: 31067474 RIS Download

Research resources used in this publication

pSpCas9(BB)-2A-Puro (PX459) V2.0 (RRID:Addgene_62988) (plasmid)

Additional research tools detected in this publication

Antibodies used in this publication

Associated grants

Agency: Wellcome Trust, United Kingdom
Agency: Wellcome Trust, United Kingdom
Id: 100140
Agency: Wellcome Trust, United Kingdom
Id: 090315
Agency: Wellcome Trust, United Kingdom
Id: 108070/Z/15/Z

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