Systems Analysis of Protein Fatty Acylation in Herpes Simplex Virus-Infected Cells Using Chemical Proteomics

Chem Biol. 2015 Aug 20;22(8):1008-17. doi: 10.1016/j.chembiol.2015.06.024. Epub 2015 Aug 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Cells, Cultured
  • Herpes Simplex / metabolism*
  • High-Throughput Screening Assays / methods
  • Humans
  • Lipoylation
  • Myristic Acid
  • Pigment Epithelium of Eye / cytology
  • Proteome / chemistry
  • Proteome / metabolism
  • Proteomics / methods*
  • Simplexvirus / metabolism*
  • Systems Analysis
  • Viral Proteins / metabolism

Substances

  • Proteome
  • Viral Proteins
  • Myristic Acid