title: HIV-1 induces the first signal to activate the NLRP3 inflammasome in monocyte-derived macrophages.
abstract: OBJECTIVE
  Inflammasomes are multimolecular complexes that regulate caspase-1. They act as sensors for endogenous and exogenous signals, and mediate the processing of pro-IL-1β into its secreted, biologically active form. The NLRP3 inflammasome and IL-1β are particularly interesting because they are required for efficient control of viral infections. Indeed, HIV-1 induces expression of NLRP3 and IL-1β in healthy controls, but not in HIV-1-infected patients. Here we evaluate whether HIV-1 can induce activation of the NLRP3 inflammasome.
  
  
  METHODS
  Human primary monocyte-derived macrophages were infected with HIV-1 in the absence or presence of classical NLRP3 inflammasome activators, and IL-1β release was assessed by ELISA.
  
  
  RESULTS
  HIV-1 initiates the priming signal for NLRP3 inflammasome activation through the NF-κB-associated pathway in human primary monocyte-derived macrophages. Furthermore, priming of NLRP3 activation in response to HIV-1 was independent of the viral envelope, since similar results were observed with HIV-1 and pseudotyped HIV-1 lacking the env gene.
  
  
  CONCLUSIONS
  Our findings suggest that HIV-1 infection promotes IL-1β secretion by inducing the first signal for NLRP3 inflammasome activation, a phenomenon that may contribute to AIDS progression.
authors.affiliation: Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellin, Colombia.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Hernandez
authors.forename: Eicke
authors.initials: E
authors.lastname: Latz
authors.forename: Silvio
authors.initials: S
authors.lastname: Urcuqui-Inchima
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human