title: Crosstalk between coagulation and inflammation during Dengue virus infection.
abstract: Dengue fever is the most prevalent viral disease transmitted by vectors (Aedes aegypti, Aedes albopictus) in worldwide. More than 100 million cases occur annually with a mortality rate of 5% and no safe vaccine is available. The pathogenesis of Dengue, where host and viral factors participate in the establishment of Dengue haemorrhagic fever (DHF) and Dengue shock syndrome (DSS) remains unresolved. Clinical observations have revealed significant abnormalities in coagulation and inflammation systems, with increased levels of tissue factor (TF) and the chemokine IL-8, correlating with the severity of the disease and implicating damage to endothelial vascular cells (EVC). Here we present novel insights concerning the crosstalk between the regulatory signaling pathways of the coagulation-inflammation processes, during Dengue virus (DV) infection of EVC. We found that DV up-regulates Protease Activated receptor type-1 (inflammation) and TF (coagulation) receptors, via the phosphorylation of p38 and ERK1/2 MAPKs, which favor the activation of NF-kappaB transcription factor. This induces pro-inflammatory (IL-8) or pro-adhesive (VCAM-1) gene expression which may lead to EVC activation. The elucidation of the basic principles that signal these processes has important implications for the design of new therapeutic strategies for DHF/DSS.
authors.affiliation: Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 04510, México, D.F., Mexico City, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Huerta-Zepeda
authors.forename: Carlos
authors.initials: C
authors.lastname: Cabello-Gutiérrez
authors.forename: Jorge
authors.initials: J
authors.lastname: Cime-Castillo
authors.forename: Verónica
authors.initials: V
authors.lastname: Monroy-Martínez
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Manjarrez-Zavala
authors.forename: Margarita
authors.initials: M
authors.lastname: Gutiérrez-Rodríguez
authors.forename: Raúl
authors.initials: R
authors.lastname: Izaguirre
authors.forename: Blanca H
authors.initials: BH
authors.lastname: Ruiz-Ordaz
mesh_terms: D001777:Blood Coagulation; D002478:Cells, Cultured; D003716:Dengue Virus / Q000472:pathogenicity*; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism / Q000821:virology*; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011516:Prothrombin / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000378:metabolism; D019595:Severe Dengue / Q000097:blood / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014774:Virulence; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D016209:Interleukin-8; D016328:NF-kappa B; D044463:Receptor, PAR-1; D019010:Vascular Cell Adhesion Molecule-1; D011516:Prothrombin; D013925:Thromboplastin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D013917:Thrombin