title: Role of the myeloid differentiation primary response (MYD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF) pathways in dengue.
abstract: OBJECTIVE
  Dengue disease courses with high viremia titers and high cytokine production suggesting viral replication and active immune response that could be related to viral evasion. One of the main targets of dengue virus (DENV) is monocyte/macrophage cells; however, little information regarding viral evasive mechanisms and pathway activation in monocytes infected by DENV is available. The aim of this study was to determine the role of myeloid differentiation primary response (MyD88), TIR-domain-containing adapter- inducing interferon-β (TRIF) and NF-kB pathways in viral replication and cytokine production in human monocyte cultures infected by DENV2.
  
  
  METHODS
  In this regard Pepinh- TRIF, Pepinh- MYD and pyrrolidine dithiocarbamate (PDTC) were used to inhibit TRIF, MYD88 and NF-kB pathways. Cytokine production was measured by ELISA.
  
  
  RESULTS
  Increased DENV replication and IFNα/β, TNF-α, IL-12 and IL-18 in infected cultures at 24h were found. All of these parameters were significantly decreased after TRIF, MYD88 or NF-kB inhibition. Association analysis between viral replication and cytokine production showed high significant positive correlation in TRIF and MYD88 treated cultures.
  
  
  CONCLUSIONS
  This study shows that DENV2 induces activation of innate-immune response and transcription factors to drive viral expression and replication in the face of pro-inflammatory antiviral responses in vitro.
authors: Instituto de Investigaciones Clínicas "Dr. Américo Negrette", Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela; Cátedra de Bioquímica General, Escuela de Bioanálisis, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela; Sociedad Venezolana de Microbiología.
authors: Anyelo
authors: A
authors: Duran
authors: Instituto de Investigaciones Clínicas "Dr. Américo Negrette", Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela; Sociedad Venezolana de Microbiología. Electronic address: valero.nereida@gmail.com.
authors: Nereida
authors: N
authors: Valero
authors: Instituto de Investigaciones Clínicas "Dr. Américo Negrette", Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
authors: Jesus
authors: J
authors: Mosquera
authors: Instituto de Investigaciones Clínicas "Dr. Américo Negrette", Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
authors: Lineth
authors: L
authors: Delgado
authors: Servicio de Enfermedades del Sistema Inmune y Oncología, Hospital Universitario "Príncipe de Asturias", Universidad de Alcalá, Madrid, Spain.
authors: Melchor
authors: M
authors: Alvarez-Mon
authors: Instituto de Investigaciones Clínicas "Dr. Américo Negrette", Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela.
authors: Mariana
authors: M
authors: Torres
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D002478:Cells, Cultured; D003715:Dengue / Q000503:physiopathology*; D003716:Dengue Virus / Q000502:physiology; D006801:Humans; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D014779:Virus Replication
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C470409:TICAM1 protein, human
keywords: Cytokines; Dengue; MYD88; TRIF; Transcription factors; Viral replication