Image_2_Dengue Virus Serotype 2 and Its Non-Structural Proteins 2A and 2B Activate NLRP3 Inflammasome.TIFF
Dengue is the most prevalent and rapidly transmitted mosquito-borne viral disease of humans. One of the fundamental innate immune responses to viral infections includes the processing and release of pro-inflammatory cytokines such as interleukin (IL-1β and IL-18) through the activation of inflammasome. Dengue virus stimulates the Nod-like receptor (NLRP3-specific inflammasome), however, the specific mechanism(s) by which dengue virus activates the NLRP3 inflammasome is unknown. In this study, we investigated the activation of the NLRP3 inflammasome in endothelial cells (HMEC-1) following dengue virus infection. Our results showed that dengue infection as well as the NS2A and NS2B protein expression increase the NLRP3 inflammasome activation, and further apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) oligomerization, and IL-1β secretion through caspase-1 activation. Specifically, we have demonstrated that NS2A and NS2B, two proteins of dengue virus that behave as putative viroporins, were sufficient to stimulate the NLRP3 inflammasome complex in lipopolysaccharide (LPS)-primed endothelial cells. In summary, our observations provide insight into the dengue-induced inflammatory response mechanism and highlight the importance of DENV-2 NS2A and NS2B proteins in activation of the NLRP3 inflammasome during dengue virus infection.
History
References
- https://doi.org//10.1056/NEJMcibr1005904
- https://doi.org//10.1086/514048
- https://doi.org//10.1186/1471-2334-8-86
- https://doi.org//10.1111/imm.12748
- https://doi.org//10.1055/s-0037-1612941
- https://doi.org//10.1074/jbc.M115.664136
- https://doi.org//10.7705/biomedica.v30i4.297
- https://doi.org//10.1111/j.1348-0421.2009.00148.x
- https://doi.org//10.1146/annurev-immunol-031210-101405
- https://doi.org//10.4049/jimmunol.1100229
- https://doi.org//10.1182/blood-2012-05-430090
- https://doi.org//10.1182/blood-2013-05-504449
- https://doi.org//10.3390/v7072777
- https://doi.org//10.3390/v7062771
- https://doi.org//10.3390/v7102866
- https://doi.org//10.3390/v7072786
- https://doi.org//10.1128/mBio.00265-10
- https://doi.org//10.1016/S0014-5793(02)03851-6
- https://doi.org//10.1371/journal.ppat.1002857
- https://doi.org//10.1371/journal.ppat.1000801
- https://doi.org//10.1128/JVI.71.8.6214-6217.1997
- https://doi.org//10.1371/journal.pone.0011112
- https://doi.org//10.1093/emboj/16.12.3519
- https://doi.org//10.1146/annurev-virology-100114-054846
- https://doi.org//10.1038/nmicrobiol.2017.37
- https://doi.org//10.1371/journal.ppat.1005350
- https://doi.org//10.1186/s12985-015-0456-4
- https://doi.org//10.1080/21505594.2017.1356540
- https://doi.org//10.1128/JVI.00002-08
- https://doi.org//10.1128/JVI.02424-12
- https://doi.org//10.1128/JVI.02882-14
- https://doi.org//10.1021/jp504911r
- https://doi.org//10.1016/j.cyto.2019.154780
- https://doi.org//10.1128/JVI.00996-19
- https://doi.org//10.1099/0022-1317-69-6-1391
- https://doi.org//10.1371/journal.pone.0090704
- https://doi.org//10.3109/08820139.2013.833622
- https://doi.org//10.4049/jimmunol.0901363
- https://doi.org//10.1016/j.cytogfr.2011.10.001
- https://doi.org//10.1016/j.imbio.2008.11.007
- https://doi.org//10.1016/j.chom.2009.03.007
- https://doi.org//10.1111/j.1462-5822.2007.01057.x
- https://doi.org//10.1155/2013/738794
- https://doi.org//10.1038/nature09663
- https://doi.org//10.1016/j.immuni.2012.01.009
- https://doi.org//10.1038/ni.1980
- https://doi.org//10.4049/jimmunol.1301490
- https://doi.org//10.1038/cr.2011.20
- https://doi.org//10.1080/10715760802582183
- https://doi.org//10.1161/CIRCRESAHA.109.214601
- https://doi.org//10.1038/sj.icb.7100008
- https://doi.org//10.1099/vir.0.19652-0
- https://doi.org//10.1002/jmv.21486
- https://doi.org//10.1038/ni.3015
- https://doi.org//10.1016/j.coi.2008.01.002
- https://doi.org//10.1016/j.virol.2015.02.017
- https://doi.org//10.1189/jlb.0312132
- https://doi.org//10.1016/j.tim.2014.09.007
- https://doi.org//10.1371/journal.pone.0032270
- https://doi.org//10.1371/journal.ppat.1003330
- https://doi.org//10.1371/journal.ppat.1003039
- https://doi.org//10.3389/fcimb.2018.00225
- https://doi.org//10.1016/j.cell.2016.03.046
- https://doi.org//10.1016/j.tibs.2016.09.002
- https://doi.org//10.1016/j.immuni.2007.03.008
- https://doi.org//10.1038/ni.1631
- https://doi.org//10.1074/jbc.M608083200
- https://doi.org//10.1038/ni.1831
- https://doi.org//10.1016/j.meegid.2015.03.025
- https://doi.org//10.1128/JVI.00354-15
- https://doi.org//10.1073/pnas.1117765109
Usage metrics
Read the peer-reviewed publication
Categories
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity
CC BY 4.0