title: Cellular visualization of macrophage pyroptosis and interleukin-1β release in a viral hemorrhagic infection in zebrafish larvae.
abstract: Hemorrhagic viral diseases are distributed worldwide with important pathogens, such as dengue virus or hantaviruses. The lack of adequate in vivo infection models has limited the research on viral pathogenesis and the current understanding of the underlying infection mechanisms. Although hemorrhages have been associated with the infection of endothelial cells, other cellular types could be the main targets for hemorrhagic viruses. Our objective was to take advantage of the use of zebrafish larvae in the study of viral hemorrhagic diseases, focusing on the interaction between viruses and host cells. Cellular processes, such as transendothelial migration of leukocytes, virus-induced pyroptosis of macrophages. and interleukin-1β (Il-1β) release, could be observed in individual cells, providing a deeper knowledge of the immune mechanisms implicated in the disease. Furthermore, the application of these techniques to other pathogens will improve the current knowledge of host-pathogen interactions and increase the potential for the discovery of new therapeutic targets. Importance: Pathogenic mechanisms of hemorrhagic viruses are diverse, and most of the research regarding interactions between viruses and host cells has been performed in cell lines that might not be major targets during natural infections. Thus, viral pathogenesis research has been limited because of the lack of adequate in vivo infection models. The understanding of the relative pathogenic roles of the viral agent and the host response to the infection is crucial. This will be facilitated by the establishment of in vivo infection models using organisms such as zebrafish, which allows the study of the diseases in the context of a complete individual. The use of this animal model with other pathogens could improve the current knowledge on host-pathogen interactions and increase the potential for the discovery of new therapeutic targets against diverse viral diseases.
authors.affiliation: Marine Research Institute, CSIC, Vigo, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Varela
authors.affiliation: Marine Research Institute, CSIC, Vigo, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Romero
authors.affiliation: Marine Research Institute, CSIC, Vigo, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Dios
authors.affiliation: Institute of Biology, Leiden University, Leiden, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van der Vaart
authors.affiliation: Marine Research Institute, CSIC, Vigo, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Figueras
authors.affiliation: Institute of Biology, Leiden University, Leiden, The Netherlands.
authors.forename: Annemarie H
authors.initials: AH
authors.lastname: Meijer
authors.affiliation: Marine Research Institute, CSIC, Vigo, Spain beatriznovoa@iim.csic.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Novoa
mesh_terms: D000818:Animals; D017209:Apoptosis; D020287:In Situ Nick-End Labeling; D053583:Interleukin-1beta / Q000378:metabolism*; D007814:Larva / Q000378:metabolism* / Q000821:virology; D008264:Macrophages / Q000276:immunology*; D015027:Zebrafish / Q000254:growth & development*
chemical_list: D053583:Interleukin-1beta
references.citation: J Interferon Cytokine Res. 2010 Dec;30(12):893-900
references.pmid: 20879862
references.citation: Trends Microbiol. 2013 Aug;21(8):380-8
references.pmid: 23830563
references.citation: Cell Microbiol. 2009 May;11(5):755-68
references.pmid: 19207728
references.citation: Dis Model Mech. 2013 Mar;6(2):383-96
references.pmid: 22956347
references.citation: Annu Rev Pathol. 2013 Jan 24;8:411-40
references.pmid: 23121052
references.citation: Dev Comp Immunol. 2012 May;37(1):97-106
references.pmid: 22107841
references.citation: Dev Biol. 2002 Aug 15;248(2):307-18
references.pmid: 12167406
references.citation: Dis Aquat Organ. 2002 Dec 10;52(3):261-72
references.pmid: 12553453
references.citation: Semin Immunol. 2013 Dec 15;25(6):425-9
references.pmid: 24201029
references.citation: Infect Immun. 2012 Aug;80(8):2878-85
references.pmid: 22689811
references.citation: Zebrafish. 2010 Jun;7(2):181-7
references.pmid: 20441522
references.citation: Nat Immunol. 2010 Dec;11(12):1136-42
references.pmid: 21057511
references.citation: Development. 1999 Sep;126(17):3735-45
references.pmid: 10433904
references.citation: J Exp Med. 1977 Jul 1;146(1):218-29
references.pmid: 195000
references.citation: PLoS One. 2011 Mar 14;6(3):e17848
references.pmid: 21423754
references.citation: PLoS Pathog. 2013;9(9):e1003619
references.pmid: 24039582
references.citation: PLoS Biol. 2006 Jan;4(1):e10
references.pmid: 16336046
references.citation: Cell Host Microbe. 2010 Jul 22;8(1):7-11
references.pmid: 20638636
references.citation: Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):223-32
references.pmid: 18162609
references.citation: J Innate Immun. 2013;5(4):367-76
references.pmid: 23635943
references.citation: Dev Comp Immunol. 2009 Nov;33(11):1212-7
references.pmid: 19619578
references.citation: J Cell Sci. 2012 Jun 1;125(Pt 11):2604-14
references.pmid: 22427689
references.citation: Curr Opin Microbiol. 2013 Jun;16(3):319-26
references.pmid: 23707339
references.citation: Circ Res. 2009 Jul 31;105(3):223-30
references.pmid: 19644057
references.citation: Cell Death Differ. 2007 Sep;14(9):1590-604
references.pmid: 17599095
references.citation: Nat Immunol. 2010 Jan;11(1):63-9
references.pmid: 19915568
references.citation: Dev Comp Immunol. 2010 May;34(5):546-52
references.pmid: 20045026
references.citation: Methods Cell Biol. 2011;105:273-308
references.pmid: 21951535
references.citation: BMC Genomics. 2010 Sep 27;11:518
references.pmid: 20875106
references.citation: Mol Biol Cell. 2014 Jan;25(1):76-86
references.pmid: 24173717
references.citation: PLoS Pathog. 2010 Feb 26;6(2):e1000661
references.pmid: 20195505
references.citation: Mol Cell Biol. 2000 Aug;20(15):5643-52
references.pmid: 10891501
references.citation: Int J Biochem Cell Biol. 2005 Aug;37(8):1560-6
references.pmid: 15896665
references.citation: Virulence. 2012 May 1;3(3):262-70
references.pmid: 22546900
references.citation: Blood. 2011 Oct 13;118(15):4102-10
references.pmid: 21849483
references.citation: Cell. 2010 Mar 19;140(6):871-82
references.pmid: 20303877
references.citation: J Gen Virol. 2013 Oct;94(Pt 10):2215-2220
references.pmid: 23884363
references.citation: J Immunol. 2007 Mar 15;178(6):3837-45
references.pmid: 17339483
references.citation: J Cell Sci. 2013 Jun 15;126(Pt 12):2545-9
references.pmid: 23781019
references.citation: Zebrafish. 2008 Dec;5(4):323-33
references.pmid: 19133831
references.citation: PLoS Negl Trop Dis. 2014 Jun 12;8(6):e2858
references.pmid: 24921924
references.citation: J Vis Exp. 2012 Mar 15;(61):
references.pmid: 22453760
references.citation: PLoS One. 2014 Jun 20;9(6):e100015
references.pmid: 24950240
references.citation: Dev Cell. 2005 Jan;8(1):97-108
references.pmid: 15621533
references.citation: PLoS Pathog. 2011 Feb 03;7(2):e1001269
references.pmid: 21304884
references.citation: PLoS Pathog. 2013;9(4):e1003330
references.pmid: 23633957
references.citation: J Pathol. 2012 Aug;227(4):431-45
references.pmid: 22374800
references.citation: Prev Vet Med. 2013 Aug 1;111(1-2):156-64
references.pmid: 23597621
references.citation: PLoS One. 2013 Sep 10;8(9):e75175
references.pmid: 24040398
references.citation: Trends Immunol. 2003 Jun;24(6):327-34
references.pmid: 12810109
references.citation: Dev Biol. 2007 Mar 15;303(2):772-83
references.pmid: 17125762
references.citation: J Immunol. 2007 Apr 1;178(7):4385-94
references.pmid: 17371995
references.citation: ILAR J. 2012;53(2):135-43
references.pmid: 23382345
references.citation: Nat Immunol. 2010 May;11(5):404-10
references.pmid: 20383149
references.citation: Immunol Rev. 2011 Sep;243(1):206-14
references.pmid: 21884178
references.citation: Hum Pathol. 2014 Jun;45(6):1221-33
references.pmid: 24767772
references.citation: PLoS One. 2012;7(8):e41635
references.pmid: 22927911
references.citation: Nature. 2013 Apr 25;496(7446):498-503
references.pmid: 23594743
references.citation: Nat Immunol. 2006 Feb;7(2):131-7
references.pmid: 16424890
references.citation: PLoS One. 2013 Jun 20;8(6):e66859
references.pmid: 23818968
references.citation: J Biol Chem. 2003 Feb 7;278(6):4268-76
references.pmid: 12464617
references.citation: Nat Rev Immunol. 2013 Aug;13(8):551-65
references.pmid: 23846113
references.citation: Annu Rev Pathol. 2006;1:171-98
references.pmid: 18039112