The Inflammasome Pathway is Activated by Dengue Virus Non-structural Protein 1 and is Protective During Dengue Virus Infection.
| Title: | The Inflammasome Pathway is Activated by Dengue Virus Non-structural Protein 1 and is Protective During Dengue Virus Infection. |
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| Authors: | Wong MP; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Infectious Diseases and Immunity Graduate Group, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Juan EYW; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Chelluri SS; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Wang P; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Pahmeier F; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Infectious Diseases and Immunity Graduate Group, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Castillo-Rojas B; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Blanc SF; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Biering SB; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Vance RE; Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology University of California, Berkeley, Berkeley, CA, USA.; Howard Hughes Medical Institute, University of California, Berkeley, California, USA.; Harris E; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Infectious Diseases and Immunity Graduate Group, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.; Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology University of California, Berkeley, Berkeley, CA, USA. |
| Source: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Sep 21. Date of Electronic Publication: 2023 Sep 21. |
| Publication Type: | Preprint; Journal Article |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| Abstract: | Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play. Here we report that DENV NS1 can trigger activation of inflammasomes, a family of cytosolic innate immune sensors that respond to infectious and noxious stimuli, in mouse and human macrophages. DENV NS1 induces the release of IL-1β in a caspase-1 dependent manner. Additionally, we find that DENV NS1-induced inflammasome activation is independent of the NLRP3, Pyrin, and AIM2 inflammasome pathways, but requires CD14. Intriguingly, DENV NS1-induced inflammasome activation does not induce pyroptosis and rapid cell death; instead, macrophages maintain cellular viability while releasing IL-1β. Lastly, we show that caspase-1/11-deficient, but not NLRP3-deficient, mice are more susceptible to lethal DENV infection. Together, these results indicate that the inflammasome pathway acts as a sensor of DENV NS1 and plays a protective role during infection. |
| Competing Interests: | Declaration of Interests R.E.V. consults for Ventus Therapeutics and X-biotix Therapeutics. |
| Comments: | Update in: PLoS Pathog. 2024 Apr 25;20(4):e1012167. doi: 10.1371/journal.ppat.1012167.. (PMID: 38662771) |
| Grant Information: | R01 AI124493 United States AI NIAID NIH HHS; R01 AI168003 United States AI NIAID NIH HHS |
| Entry Date(s): | Date Created: 20231004 Latest Revision: 20240507 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10543007 |
| DOI: | 10.1101/2023.09.21.558875 |
| PMID: | 37790301 |
| Database: | MEDLINE |
Preprint; Journal Article