Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

Virology. 2015 Nov:485:58-78. doi: 10.1016/j.virol.2015.06.024. Epub 2015 Jul 23.

Abstract

Background: Borna disease virus (BDV) is a neurotropic RNA virus persistently infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key protein post-translational modification (PTM). The unexpectedly broad regulatory scope of Kac let us to profile the entire acetylome upon BDV infection.

Methods: The acetylome was profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics.

Results: We identified and quantified 791 Kac sites in 473 Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL) cells. Bioinformatic analysis revealed that BDV infection alters the acetylation of metabolic proteins, membrane-associated proteins and transmembrane transporter activity, and affects the acetylation of several lysine acetyltransferases (KAT).

Conclusions: Upon BDV persistence the OL acetylome is manipulated towards higher energy and transporter levels necessary for shuttling BDV proteins to and from nuclear replication sites.

Keywords: Acetylation; BDV; Borna disease virus; Kac; Oligodendroglia; Proteomic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Amino-Acid N-Acetyltransferase / genetics
  • Amino-Acid N-Acetyltransferase / metabolism*
  • Borna disease virus / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Computational Biology
  • Energy Metabolism
  • Fetus
  • Host-Pathogen Interactions
  • Humans
  • Isotope Labeling
  • Lysine / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Annotation
  • Molecular Sequence Data
  • Oligodendroglia / metabolism*
  • Oligodendroglia / virology
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational*
  • Proteome / genetics
  • Proteome / metabolism*
  • Virus Replication

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Proteome
  • Amino-Acid N-Acetyltransferase
  • Lysine