Proteomic Analysis Uncovers Measles Virus Protein C Interaction With p65-iASPP Protein Complex

Mol Cell Proteomics. 2021;20:100049. doi: 10.1016/j.mcpro.2021.100049. Epub 2021 Jan 27.

Abstract

Viruses manipulate the central machineries of host cells to their advantage. They prevent host cell antiviral responses to create a favorable environment for their survival and propagation. Measles virus (MV) encodes two nonstructural proteins MV-V and MV-C known to counteract the host interferon response and to regulate cell death pathways. Several molecular mechanisms underlining MV-V regulation of innate immunity and cell death pathways have been proposed, whereas MV-C host-interacting proteins are less studied. We suggest that some cellular factors that are controlled by MV-C protein during viral replication could be components of innate immunity and the cell death pathways. To determine which host factors are targeted by MV-C, we captured both direct and indirect host-interacting proteins of MV-C protein. For this, we used a strategy based on recombinant viruses expressing tagged viral proteins followed by affinity purification and a bottom-up mass spectrometry analysis. From the list of host proteins specifically interacting with MV-C protein in different cell lines, we selected the host targets that belong to immunity and cell death pathways for further validation. Direct protein interaction partners of MV-C were determined by applying protein complementation assay and the bioluminescence resonance energy transfer approach. As a result, we found that MV-C protein specifically interacts with p65-iASPP protein complex that controls both cell death and innate immunity pathways and evaluated the significance of these host factors on virus replication.

Keywords: Measles; cell death; innate immunity; virulence factors; virus-host protein-protein interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death
  • Cell Line
  • Chlorocebus aethiops
  • Host-Pathogen Interactions
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Measles virus / genetics
  • Measles virus / physiology
  • Protein Interaction Maps
  • Proteomics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication

Substances

  • C protein, measles virus
  • Intracellular Signaling Peptides and Proteins
  • PPP1R13L protein, human
  • Repressor Proteins
  • Transcription Factor RelA
  • Tumor Suppressor Protein p53
  • Viral Nonstructural Proteins