Quantitative Proteomics Reveals the Roles of Peroxisome-associated Proteins in Antiviral Innate Immune Responses

Mol Cell Proteomics. 2015 Sep;14(9):2535-49. doi: 10.1074/mcp.M115.048413. Epub 2015 Jun 29.

Abstract

Compared with whole-cell proteomic analysis, subcellular proteomic analysis is advantageous not only for the increased coverage of low abundance proteins but also for generating organelle-specific data containing information regarding dynamic protein movement. In the present study, peroxisome-enriched fractions from Sendai virus (SeV)-infected or uninfected HepG2 cells were obtained and subjected to quantitative proteomics analysis. We identified 311 proteins that were significantly changed by SeV infection. Among these altered proteins, 25 are immune response-related proteins. Further bioinformatic analysis indicated that SeV infection inhibits cell cycle-related proteins and membrane attack complex-related proteins, all of which are beneficial for the survival and replication of SeV within host cells. Using Luciferase reporter assays on several innate immune-related reporters, we performed functional analysis on 11 candidate proteins. We identified LGALS3BP and CALU as potential negative regulators of the virus-induced activation of the type I interferons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / metabolism*
  • Calcium-Binding Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Computational Biology / methods
  • Gene Expression Regulation
  • Glycoproteins / metabolism*
  • Hep G2 Cells
  • Humans
  • Immunity, Innate
  • Interferons / metabolism
  • Peroxisomes / metabolism*
  • Proteomics / methods*
  • Respirovirus Infections / immunology*
  • Sendai virus / immunology*
  • Virus Replication

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CALU protein, human
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Glycoproteins
  • LGALS3BP protein, human
  • Interferons