Participation of the Dengue virus in the fibrinolytic process.
To date, the phatophysiology of hemorrhagic dengue is still unknown and hypotheses which aim to explain the unfortunate cases of the disease (hemorrhagic fever/shock syndrome) are based on epidemiological data and favor the notion of the participation of heterotypic non-neutralizing antibodies during the course of secondary infection (immunologic status of the host). However, cases of hemorrhagic dengue have been reported during the course of primary infections. We propose that the dengue virus, specifically the envelope glycoprotein can participate directly in the installation of the hemorrhagic phenomenon by means of the binding and activation of plasminogen (PLG) as condition previous to the development of the fibrinolytic process. Based on this hypothesis, we evaluated the biological activity of some viral isolates proceeding from hemorrhagic and from dengue fever cases in an in vitro model of fibrinolysis. Dengue isolates were capable of activating PLG. The plasmin generated specifically degraded the fibrin/fibrinogen molecule. This catalytic process can be prevented by the presence of the specific plasmin inhibitor, alpha-2-antiplasmin, for virus isolates from dengue fever, but not for isolates associated with dengue hemorrhagic disease, favoring the exacerbation of the fibrinolytic activity. This new approach allows us to suggest the importance of viral factors in the dengue hemorrhagic fever.
Monroy
V
V
Departamento de Biología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, DF, México.
Ruiz
B H
BH
D000595:Amino Acid Sequence; D000818:Animals; D000933:Antifibrinolytic Agents; D002460:Cell Line; D002522:Chlorocebus aethiops; D003715:Dengue / Q000821:virology; D003716:Dengue Virus / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000378:metabolism*; D019595:Severe Dengue / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism; D000979:alpha-2-Antiplasmin
D000933:Antifibrinolytic Agents; D014764:Viral Proteins; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D010958:Plasminogen