Impact of Influenza A Virus Infection on the Proteomes of Human Bronchoepithelial Cells from Different Donors

J Proteome Res. 2017 Sep 1;16(9):3287-3297. doi: 10.1021/acs.jproteome.7b00286. Epub 2017 Aug 16.

Abstract

Susceptibility to influenza A virus is determined by a balance of viral and host factors. The genetic background of the host contributes to the severity of disease, but the influenza-related proteomes of cells from different individuals have not been compared. We used high-resolution mass spectrometry to identify proteins in normal human bronchial epithelial (NHBE) cells isolated from three different donors. Infection of each NHBE cell culture with influenza A/California/07/2009 (H1N1) resulted in expression of viral proteins and a variety of host proteins, including interferons, interferon-stimulated genes, and secreted chemokines/cytokines. The expression level of viral proteins corresponded to the level of host proteins that support influenza infection (i.e., pro-viral proteins); however, production of infectious virus was inversely related to the levels of antiviral proteins, suggesting that a balance of pro-viral proteins and the antiviral response controls virus replication. In summary, our results demonstrate that expression levels of pro-viral as well as antiviral factors are different for each donor and suggest that relative quantitation of these factors may provide a way to identify individuals or population groups who are susceptible to severe influenza disease.

Keywords: cytokines; human airway epithelial cells; influenza; interferons; metallothionein; proteome; superoxide dismutase; trypsin; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / genetics
  • Cytokines / immunology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Gene Expression Regulation
  • Host-Pathogen Interactions*
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza A Virus, H1N1 Subtype / metabolism
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology
  • Interferons / genetics
  • Interferons / immunology
  • Metallothionein / genetics
  • Metallothionein / immunology
  • Molecular Sequence Annotation
  • Primary Cell Culture
  • Proteome / genetics*
  • Proteome / immunology
  • Proteomics / instrumentation
  • Proteomics / methods
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / virology
  • Signal Transduction
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / immunology
  • Ubiquitin / genetics
  • Ubiquitin / immunology
  • Viral Load
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism

Substances

  • Cytokines
  • Interferon Regulatory Factors
  • Proteome
  • Ubiquitin
  • Viral Proteins
  • Interferons
  • Metallothionein
  • Superoxide Dismutase