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Thromb Haemost 2008; 99(05): 936-943
DOI: 10.1160/TH07-08-0483
Wound Healing and Inflammation/Infection
Schattauer GmbH

Crosstalk between coagulation and inflammation during Dengue virus infection

Alejandra Huerta-Zepeda
1   Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico
,
Carlos Cabello-Gutiérrez
1   Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico
,
Jorge Cime-Castillo
1   Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico
,
Verónica Monroy-Martínez
1   Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico
,
Maria Eugenia Manjarrez-Zavala
2   Departamento de Virología, Instituto Nacional de Enfermedades Respiratorias, México D.F., México
,
Margarita Gutiérrez-Rodríguez
3   Departamento de Bioquímica, Hospital de Especialidades, Centro Médico Siglo XXI, IMSS, México D.F., México
,
Raú Izaguirre
4   Departamento de Hematología, Hospital de Cardiología “Ignacio Chávez” SSA, México D.F., México
,
Blanca H. Ruiz-Ordaz
1   Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico
› Author AffiliationsThe present study was supported in part by the PAPIIT and CONACYT programs.
Further Information

Publication History

Received 01 August 2007

Accepted after major revision 23 March 2008

Publication Date:
30 November 2017 (online)

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Summary

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-κB 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.

keywords

Dengue virus - tissue factor - PAR-1 - endothelial cell - crosstalk - coagulation-inflammation
 

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