title: Efficacy of IFN-λ1 to protect human airway epithelial cells against human rhinovirus 1B infection.
abstract: Impaired interferon (IFN) production has been observed in various obstructive respiratory diseases. This contributes to enhanced sensitivity towards viral infections triggering acute exacerbations. To compensate for this impaired host IFN response, there is need to explore new therapeutic strategies, like exogenous administration of IFNs as prophylactic treatment. In the present study, we examined the protective potential of IFN-λ1 and compared it with the previously established protecting effect of IFN-β. A549 cells and human primary bronchial epithelial cells were first treated with either IFN-β (500 IU/ml) or IFN-λ1 (500 ng/ml) for 18 h. For infection, two approaches were adopted: i) Continuous scenario: after pre-treatment, cells were infected immediately for 24 h with human rhinovirus 1B (HRV1B) in IFN-containing medium, or were cultured for another 72 h in IFN-containing medium, and then infected for 24 h with HRV1B, ii) Pre-treatment scenario: IFN-containing medium was replaced after 18 h and cells were infected for 4 h either immediately after pre-treatment or after additional culturing for 72 h in IFN-free medium. The protective effect was evaluated in terms of reduction in the number of viral copies/infectious progeny, and enhanced expression of IFN-stimulated genes (ISGs). In both cell types and in both approaches, IFN-λ1 and IFN-β treatment resulted in pronounced and long-lasting antiviral effects exemplified by significantly reduced viral copy numbers and diminished infectious progeny. This was associated with strong up-regulation of multiple ISGs. However, in contrast to the IFN-β induced expression of ISGs, which decreased over time, expression of ISGs induced by IFN-λ1 was sustained or even increased over time. Here we demonstrate that the protective potential of IFN-λ1 is comparable to IFN-β. Yet, the long-lasting induction of ISGs by IFN-λ1 and most likely less incitement of side effects due to more localized expression of its receptors could make it an even more promising candidate for prophylactic treatment than IFN-β.
authors.affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Fahad
authors.initials: F
authors.lastname: Gulraiz
authors.affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands; Department of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Carla
authors.initials: C
authors.lastname: Bellinghausen
authors.affiliation: Department of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Mieke A
authors.initials: MA
authors.lastname: Dentener
authors.affiliation: Department of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Niki L
authors.initials: NL
authors.lastname: Reynaert
authors.affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Giel R
authors.initials: GR
authors.lastname: Gaajetaan
authors.affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Erik V
authors.initials: EV
authors.lastname: Beuken
authors.affiliation: Department of Respiratory Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Gernot G
authors.initials: GG
authors.lastname: Rohde
authors.affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Cathrien A
authors.initials: CA
authors.lastname: Bruggeman
authors.affiliation: Department of Medical Microbiology, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Stassen
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D001980:Bronchi / Q000473:pathology*; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology* / Q000821:virology*; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000494:pharmacology / Q000627:therapeutic use*; D010850:Picornaviridae Infections / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012229:Rhinovirus / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
references.citation: J Immunol. 2007 Sep 15;179(6):3434-42
references.pmid: 17785777
references.citation: Immunity. 2013 May 23;38(5):1025-37
references.pmid: 23623383
references.citation: J Virol. 2009 Apr;83(8):3834-42
references.pmid: 19193806
references.citation: Chest. 2006 Oct;130(4):1203-10
references.pmid: 17035457
references.citation: J Allergy Clin Immunol. 2010 Jun;125(6):1178-87; quiz 1188-9
references.pmid: 20513517
references.citation: PLoS Pathog. 2008 Mar 14;4(3):e1000017
references.pmid: 18369468
references.citation: Curr Opin Pharmacol. 2007 Jun;7(3):252-8
references.pmid: 17369093
references.citation: Cancer Biol Ther. 2008 Jul;7(7):1109-15
references.pmid: 18698163
references.citation: Virology. 2008 May 10;374(2):399-410
references.pmid: 18272195
references.citation: J Virol. 2010 Nov;84(21):11515-22
references.pmid: 20739515
references.citation: J Exp Med. 2005 Mar 21;201(6):937-47
references.pmid: 15781584
references.citation: Annu Rev Biochem. 1998;67:227-64
references.pmid: 9759489
references.citation: Infect Immun. 2011 Oct;79(10):4131-45
references.pmid: 21825067
references.citation: Thorax. 2003 Jan;58(1):37-42
references.pmid: 12511718
references.citation: Infect Immun. 2011 Sep;79(9):3733-43
references.pmid: 21690236
references.citation: Am J Respir Crit Care Med. 2011 Mar 15;183(6):734-42
references.pmid: 20889904
references.citation: J Infect. 2013 Feb;66(2):163-9
references.pmid: 23201152
references.citation: Eur Respir J. 2010 Sep;36(3):646-54
references.pmid: 20150207
references.citation: J Gen Virol. 2008 Jan;89(Pt 1):1-47
references.pmid: 18089727
references.citation: Nat Med. 2006 Sep;12(9):1023-6
references.pmid: 16906156
references.citation: Lancet. 2002 Mar 9;359(9309):831-4
references.pmid: 11897281
references.citation: Natl Health Stat Report. 2011 Jan 12;(32):1-14
references.pmid: 21355352
references.citation: Eur Respir J. 2000 Oct;16(4):677-83
references.pmid: 11106212
references.citation: FEBS Lett. 1998 Dec 11;441(1):106-10
references.pmid: 9877175
references.citation: J Viral Hepat. 2012 Feb;19(2):e154-62
references.pmid: 22239513
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Antiviral Res. 2012 Jan;93(1):39-47
references.pmid: 22057305
references.citation: Am J Physiol Lung Cell Mol Physiol. 2000 Jan;278(1):L51-8
references.pmid: 10645890
references.citation: Am J Respir Crit Care Med. 2006 May 15;173(10):1114-21
references.pmid: 16484677
references.citation: PLoS Pathog. 2008 Sep 12;4(9):e1000151
references.pmid: 18787692
references.citation: J Allergy Clin Immunol. 2005 Aug;116(2):267-73
references.pmid: 16083778
references.citation: Clin Microbiol Rev. 2011 Jan;24(1):210-29
references.pmid: 21233513
references.citation: J Virol. 2010 Sep;84(18):9140-8
references.pmid: 20592090
references.citation: J Virol. 2010 Jun;84(11):5670-7
references.pmid: 20335250
references.citation: PLoS Pathog. 2010 Nov 04;6(11):e1001178
references.pmid: 21079690
references.citation: Virus Res. 2011 Sep;160(1-2):360-6
references.pmid: 21816185
references.citation: J Virol. 2009 Nov;83(22):11581-7
references.pmid: 19740998
references.citation: J Virol Methods. 2009 Oct;161(1):147-53
references.pmid: 19524621
references.citation: J Virol. 2006 May;80(9):4501-9
references.pmid: 16611910
references.citation: J Virol. 2007 Sep;81(18):9790-800
references.pmid: 17626092
references.citation: Nature. 2005 Apr 7;434(7034):772-7
references.pmid: 15800576
references.citation: J Virol. 2002 Sep;76(18):9060-8
references.pmid: 12186889
references.citation: J Biol Chem. 2003 Jul 18;278(29):26589-96
references.pmid: 12732645
references.citation: Respir Res. 2013 Feb 06;14:15
references.pmid: 23384071
references.citation: Nat Immunol. 2003 Jan;4(1):69-77
references.pmid: 12483210
references.citation: Allergy. 2009 Mar;64(3):375-86
references.pmid: 19175599