1887

Abstract

Highly pathogenic Nipah virus (NiV) generally causes severe encephalitis in humans. Respiratory symptoms are infrequently observed, likely reflecting variations in infection kinetics in human airways. Supporting this idea, we recently identified individual differences in NiV replication kinetics in cultured airway epithelia from different human donors. As type III interferons (IFN-λ) represent major players in the defence mechanism against viral infection of the respiratory mucosa, we studied IFN-λ induction and antiviral activity in NiV-infected primary differentiated human bronchial epithelial cells (HBEpCs) cultured under air–liquid interface conditions. Our studies revealed that IFN-λ was upregulated in airway epithelia upon NiV infection. We also show that IFN-λ pretreatment efficiently inhibited NiV replication. Interestingly, the antiviral activity of IFN-λ varied in HBEpCs from two different donors. Increased sensitivity to IFN-λ was associated with higher expression levels of IFN-λ receptors, enhanced phosphorylation of STAT1, as well as enhanced induction of interferon-stimulated gene expression. These findings suggest that individual variations in IFN-λ receptor expression affecting IFN responsiveness can play a functional role for NiV replication kinetics in human respiratory epithelial cells of different donors.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000934
2017-10-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/10/2447.html?itemId=/content/journal/jgv/10.1099/jgv.0.000934&mimeType=html&fmt=ahah

References

  1. Chua KB, Bellini WJ, Rota PA, Harcourt BH, Tamin A et al. Nipah virus: a recently emergent deadly paramyxovirus. Science 2000; 288:1432–1435 [View Article][PubMed]
    [Google Scholar]
  2. Lo MK, Rota PA. The emergence of Nipah virus, a highly pathogenic paramyxovirus. J Clin Virol 2008; 43:396–400 [View Article][PubMed]
    [Google Scholar]
  3. Escaffre O, Borisevich V, Carmical JR, Prusak D, Prescott J et al. Henipavirus pathogenesis in human respiratory epithelial cells. J Virol 2013; 87:3284–3294 [View Article][PubMed]
    [Google Scholar]
  4. Escaffre O, Borisevich V, Vergara LA, Wen JW, Long D et al. Characterization of Nipah virus infection in a model of human airway epithelial cells cultured at an air-liquid interface. J Gen Virol 2016; 97:1077–1086 [View Article][PubMed]
    [Google Scholar]
  5. Egli A, Santer DM, O'Shea D, Tyrrell DL, Houghton M. The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections. Emerg Microbes Infect 2014; 3:e51 [View Article][PubMed]
    [Google Scholar]
  6. Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M et al. IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol 2003; 4:69–77 [View Article][PubMed]
    [Google Scholar]
  7. Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S et al. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 2003; 4:63–68 [View Article][PubMed]
    [Google Scholar]
  8. Lazear HM, Nice TJ, Diamond MS. Interferon-λ: immune functions at barrier surfaces and beyond. Immunity 2015; 43:15–28 [View Article][PubMed]
    [Google Scholar]
  9. Sommereyns C, Paul S, Staeheli P, Michiels T. IFN-lambda (IFN-λ) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo . PLoS Pathog 2008; 4:e1000017 [View Article][PubMed]
    [Google Scholar]
  10. Contoli M, Message SD, Laza-Stanca V, Edwards MR, Wark PA et al. Role of deficient type III interferon-λ production in asthma exacerbations. Nat Med 2006; 12:1023–1026 [View Article][PubMed]
    [Google Scholar]
  11. Mahlakõiv T, Ritz D, Mordstein M, Dediego ML, Enjuanes L et al. Combined action of type I and type III interferon restricts initial replication of severe acute respiratory syndrome coronavirus in the lung but fails to inhibit systemic virus spread. J Gen Virol 2012; 93:2601–2605 [View Article][PubMed]
    [Google Scholar]
  12. Mordstein M, Kochs G, Dumoutier L, Renauld JC, Paludan SR et al. Interferon-λ contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS Pathog 2008; 4:e1000151 [View Article][PubMed]
    [Google Scholar]
  13. Mordstein M, Neugebauer E, Ditt V, Jessen B, Rieger T et al. Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections. J Virol 2010; 84:5670–5677 [View Article][PubMed]
    [Google Scholar]
  14. Dietzel E, Kolesnikova L, Sawatsky B, Heiner A, Weis M et al. Nipah virus matrix protein influences fusogenicity and is essential for particle infectivity and stability. J Virol 2015; 90:2514–2522 [View Article][PubMed]
    [Google Scholar]
  15. Sauerhering L, Zickler M, Elvert M, Behner L, Matrosovich T et al. Species-specific and individual differences in Nipah virus replication in porcine and human airway epithelial cells. J Gen Virol 2016; 97:1511–1519 [View Article][PubMed]
    [Google Scholar]
  16. Bonaparte MI, Dimitrov AS, Bossart KN, Crameri G, Mungall BA et al. Ephrin-B2 ligand is a functional receptor for Hendra virus and Nipah virus. Proc Natl Acad Sci USA 2005; 102:10652–10657 [View Article][PubMed]
    [Google Scholar]
  17. Negrete OA, Levroney EL, Aguilar HC, Bertolotti-Ciarlet A, Nazarian R et al. EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus. Nature 2005; 436:401–405 [View Article][PubMed]
    [Google Scholar]
  18. Duong FH, Trincucci G, Boldanova T, Calabrese D, Campana B et al. IFN-λ receptor 1 expression is induced in chronic hepatitis C and correlates with the IFN-λ3 genotype and with nonresponsiveness to IFN-α therapies. J Exp Med 2014; 211:857–868 [View Article][PubMed]
    [Google Scholar]
  19. Sarkis PT, Ying S, Xu R, Yu XF. STAT1-independent cell type-specific regulation of antiviral APOBEC3G by IFN-α. J Immunol 2006; 177:4530–4540 [View Article][PubMed]
    [Google Scholar]
  20. Schlaak JF, Hilkens CM, Costa-Pereira AP, Strobl B, Aberger F et al. Cell-type and donor-specific transcriptional responses to interferon-α. Use of customized gene arrays. J Biol Chem 2002; 277:49428–49437 [View Article][PubMed]
    [Google Scholar]
  21. Gray TE, Guzman K, Davis CW, Abdullah LH, Nettesheim P. Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells. Am J Respir Cell Mol Biol 1996; 14:104–112 [View Article][PubMed]
    [Google Scholar]
  22. Freitag TC, Maisner A. Early activation of primary brain microvascular endothelial cells by Nipah virus glycoprotein-containing particles. J Virol 2015; 90:2706–2709 [View Article][PubMed]
    [Google Scholar]
  23. Krutzik PO, Nolan GP. Intracellular phospho-protein staining techniques for flow cytometry: monitoring single cell signaling events. Cytometry A 2003; 55:61–70 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000934
Loading
/content/journal/jgv/10.1099/jgv.0.000934
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error