Differentiated swine airway epithelial cell cultures for the investigation of influenza A virus infection and replication

Influenza Other Respir Viruses. 2013 Mar;7(2):139-50. doi: 10.1111/j.1750-2659.2012.00371.x. Epub 2012 Apr 25.

Abstract

Background: Differentiated human airway epithelial cell cultures have been utilized to investigate cystic fibrosis, wound healing, and characteristics of viral infections. These cultures, grown at an air-liquid interface (ALI) in media with defined hormones and growth factors, recapitulate many aspects of the in vivo respiratory tract and allow for experimental studies at the cellular level.

Objectives: To optimize growth conditions for differentiated swine airway epithelial cultures and to use these cultures to examine influenza virus infection and replication.

Methods: Primary swine respiratory epithelial cells were grown at an air-liquid interface with varying amounts of retinoic acid and epidermal growth factor. Cells grown with optimized concentrations of these factors for 4 weeks differentiated into multilayer epithelial cell cultures resembling the lining of the swine respiratory tract. Influenza virus infection and replication were examined in these cultures.

Results/conclusions: Retinoic acid promoted ciliogenesis, whereas epidermal growth factor controlled the thickness of the pseudoepithelium. The optimal concentrations for differentiated swine cell cultures were 1·5 ng/ml epidermal growth factor and 100nm retinoic acid. Influenza A viruses infected and productively replicated in these cultures in the absence of exogenous trypsin, suggesting that the cultures express a protease capable of activating influenza virus hemagglutinin. Differences in virus infection and replication characteristics found previously in pigs in vivo were recapitulated in the swine cultures. This system could be a useful tool for a range of applications, including investigating influenza virus species specificity, defining cell tropism of influenza viruses in the swine respiratory epithelium, and studying other swine respiratory diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Cells, Cultured
  • Epithelial Cells / virology*
  • Influenza A virus / growth & development
  • Influenza A virus / pathogenicity*
  • Swine
  • Virus Cultivation
  • Virus Replication