title: Systems Analysis of Protein Fatty Acylation in Herpes Simplex Virus-Infected Cells Using Chemical Proteomics.
abstract: Protein fatty acylation regulates diverse aspects of cellular function and organization and plays a key role in host immune responses to infection. Acylation also modulates the function and localization of virus-encoded proteins. Here, we employ chemical proteomics tools, bio-orthogonal probes, and capture reagents to study myristoylation and palmitoylation during infection with herpes simplex virus (HSV). Using in-gel fluorescence imaging and quantitative mass spectrometry, we demonstrate a generalized reduction in myristoylation of host proteins, whereas palmitoylation of host proteins, including regulators of interferon and tetraspanin family proteins, was selectively repressed. Furthermore, we found that a significant fraction of the viral proteome undergoes palmitoylation; we identified a number of virus membrane glycoproteins, structural proteins, and kinases. Taken together, our results provide broad oversight of protein acylation during HSV infection, a roadmap for similar analysis in other systems, and a resource with which to pursue specific analysis of systems and functions.
authors.affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
authors.forename: Remigiusz A
authors.initials: RA
authors.lastname: Serwa
authors.affiliation: Section of Virology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1QN, UK.
authors.forename: Fernando
authors.initials: F
authors.lastname: Abaitua
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle Street 10, 13125 Berlin, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Krause
authors.affiliation: Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ, UK. Electronic address: e.tate@imperial.ac.uk.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate
authors.affiliation: Section of Virology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1QN, UK. Electronic address: pohare@imperial.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: O'Hare
mesh_terms: D000215:Acylation; D002478:Cells, Cultured; D006561:Herpes Simplex / Q000378:metabolism*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D054878:Lipoylation; D019814:Myristic Acid; D010857:Pigment Epithelium of Eye / Q000166:cytology; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D018139:Simplexvirus / Q000378:metabolism*; D013597:Systems Analysis; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D020543:Proteome; D014764:Viral Proteins; D019814:Myristic Acid