title: Multiple roles of the coagulation protease cascade during virus infection.
abstract: The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.
authors.affiliation: Thrombosis and Hemostasis Program, Division of Hematology and Oncology, Department of Medicine, University of North Carolina McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC.
authors.forename: Silvio
authors.initials: S
authors.lastname: Antoniak
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D003716:Dengue Virus / Q000378:metabolism; D015942:Factor VIIa / Q000037:antagonists & inhibitors; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007113:Immunity, Innate; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D051379:Mice; D008954:Models, Biological; D009205:Myocarditis / Q000378:metabolism / Q000821:virology; D010447:Peptide Hydrolases / Q000378:metabolism*; D044463:Receptor, PAR-1 / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000378:metabolism; D015398:Signal Transduction; D013925:Thromboplastin / Q000037:antagonists & inhibitors; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014777:Virus Diseases / Q000097:blood*
chemical_list: D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D044462:Receptors, Proteinase-Activated; C519703:TLR3 protein, mouse; C493487:Tlr4 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D013925:Thromboplastin; D010447:Peptide Hydrolases; D015942:Factor VIIa