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The inflammasome pathway is activated by dengue virus non-structural protein 1 and is protective during dengue virus infection.
Wong, Marcus P; Juan, Evan Y W; Pahmeier, Felix; Chelluri, Sai S; Wang, Phoebe; Castillo-Rojas, Bryan; Blanc, Sophie F; Biering, Scott B; Vance, Russell E; Harris, Eva.
Afiliação
  • Wong MP; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • Juan EYW; Infectious Diseases and Immunity Graduate Group, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • Pahmeier F; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • Chelluri SS; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • Wang P; Infectious Diseases and Immunity Graduate Group, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • Castillo-Rojas B; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • Blanc SF; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • Biering SB; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • Vance RE; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
  • Harris E; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
PLoS Pathog ; 20(4): e1012167, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38662771
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-1ß 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-1ß. 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas não Estruturais Virais / Dengue / Vírus da Dengue / Inflamassomos / Macrófagos Limite: Animals / Humans Idioma: En Revista: PLoS Pathog Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas não Estruturais Virais / Dengue / Vírus da Dengue / Inflamassomos / Macrófagos Limite: Animals / Humans Idioma: En Revista: PLoS Pathog Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos