Tissue plasminogen activator induced by dengue virus infection of human endothelial cells

Huang, Ying-Huey; Lei, Huan‐Yao; Liu, Hsiao Sheng; Lin, Yee‐Shin; Chen, Shun Hua; Liu, Ching-Chuan; Yeh, Trai Ming

doi:10.1002/jmv.10438

Cited by 44 publications

(35 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…was also reported to stimulate the release of tPA from human endothelial cells (36). Consequently, the higher availability of PLG activators could elicit the activation of the leptospiral-bound PLG to active enzyme, triggering PLA-mediated ECM proteolysis and promoting an enhanced transmigration activity.…”

Section: Discussionmentioning

confidence: 96%

Interaction of Leptospira interrogans with Human Proteolytic Systems Enhances Dissemination through Endothelial Cells and Protease Levels

et al. 2013

View full text Add to dashboard Cite

We have recently reported the ability of Leptospira to capture plasminogen (PLG) and generate plasmin (PLA) bound on the microbial surface in the presence of exogenous activators. In this work, we examined the effects of leptospiral PLG binding for active penetration through the endothelial cell barrier and activation. The results indicate that leptospires with PLG association or PLA activation have enhanced migration activity through human umbilical vein endothelial cell (HUVEC) monolayers compared with untreated bacteria. Leptospira cells coated with PLG were capable of stimulating the expression of PLG activators by HUVECs. Moreover, leptospires endowed with PLG or PLA promoted transcriptional upregulation matrix metalloprotease 9 (MMP-9). Serum samples from patients with confirmed leptospirosis showed higher levels of PLG activators and total MMP-9 than serum samples from normal (healthy) subjects. The highest level of PLG activators and total MMP-9 was detected with microscopic agglutination test (MAT)-negative serum samples, suggesting that this proteolytic activity stimulation occurs at the early stage of the disease. Furthermore, a gelatin zymography profile obtained for MMPs with serum samples from patients with leptospirosis appears to be specific to leptospiral infection because serum samples from patients with unrelated infectious diseases produced no similar degradation bands. Altogether, the data suggest that the Leptospira-associated PLG or PLA might represent a mechanism that contributes to bacterial penetration of endothelial cells through an activation cascade of events that enhances the proteolytic capability of the organism. To our knowledge, this is the first proteolytic activity associated with leptospiral pathogenesis described to date.

show abstract

Section: Discussionmentioning

confidence: 96%

Interaction of Leptospira interrogans with Human Proteolytic Systems Enhances Dissemination through Endothelial Cells and Protease Levels

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Dengue virus infection induces endothelial production of tPA as well as IL-6. The de novo synthesis of tPA is blocked by anti-IL-6 antibodies, indicating that tPA production by endothelial cells is IL-6 dependent [48] . Furthermore, antibodies against dengue virus E protein can bind to human plasminogen.…”

Section: Dengue Virus-induced Vasculopathymentioning

confidence: 98%

Immunopathogenesis of Dengue Hemorrhagic Fever

Lei¹,

Huang²,

Lin³

et al. 2008

American J. of Infectious Diseases

Self Cite

View full text Add to dashboard Cite

Abstract:Dengue virus infection causes Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) whose pathogeneses were not clearly understood. A new hypothesis of immunopathogenesis is proposed for the development of the DHF/DSS. An aberrant immune overactivation after dengue virus infection not only impair the immune response to clear the virus, but also result in overproduction of cytokines that affect monocytes, endothelial cells, and hepatocytes, as well as the abnormal production of autoantibodies to platelet and endothelial cells. A molecular mimicry occurs between platelets/endothelial cells and dengue virus antigens. Platelets and endothelial cells are bound by the cross-reactive anti-dengue virus antibodies such as anti-NS1 or anti-prM antibodies. The IFN-γ activated macrophage would phagocytosize the osponized targets. Dengue virus-induced vasculopathy and coagulopathy are involved in the pathogenesis of hemorrhage, and the unbalance between coagulation and fibrinolysis activation increases the likelihood of severe hemorrhage in DHF/DSS. This theory of transient hemophagocytic activity in immunopathogenesis of DHF/DSS can account for specific characteristics of clinical, pathologic, and epidemiological observations in dengue virus infection.

show abstract

“…Although it is immortal, this cell line has been shown to exhibit metabolism similar to primary endothelial cells (9,32). DENV-infected endothelial cells have been found in dengue patients and murine models of DENV disease and may contribute to DENV pathogenesis (33)(34)(35)(36)(37)(38)(39)(40). Infected TIME cells treated with oxamate showed a block Relative abundance of HK2 mRNA was normalized to the abundance of GAPDH mRNA by the delta threshold cycle method.…”

Section: Denv Infection Alters Glucose Metabolismmentioning

confidence: 99%

Dengue Virus Induces and Requires Glycolysis for Optimal Replication

Fontaine

Sanchez

Camarda

et al. 2015

J Virol

249

272

View full text Add to dashboard Cite

Viruses rely on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. Dengue virus (DENV), a member of the Flaviviridae family, is one of the most important arthropod-borne human pathogens worldwide. We analyzed global intracellular metabolic changes associated with DENV infection of primary human cells. Our metabolic profiling data suggested that central carbon metabolism, particularly glycolysis, is strikingly altered during a time course of DENV infection. Glucose consumption is increased during DENV infection and depriving DENV-infected cells of exogenous glucose had a pronounced impact on viral replication. Furthermore, the expression of both glucose transporter 1 and hexokinase 2, the first enzyme of glycolysis, is upregulated in DENV-infected cells. Pharmacologically inhibiting the glycolytic pathway dramatically reduced DENV RNA synthesis and infectious virion production, revealing a requirement for glycolysis during DENV infection. Thus, these experiments suggest that DENV induces the glycolytic pathway to support efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat DENV infection in the future. IMPORTANCEApproximately 400 million people are infected with dengue virus (DENV) annually, and more than one-third of the global population is at risk of infection. As there are currently no effective vaccines or specific antiviral therapies for DENV, we investigated the impact DENV has on the host cellular metabolome to identify metabolic pathways that are critical for the virus life cycle. We report an essential role for glycolysis during DENV infection. DENV activates the glycolytic pathway, and inhibition of glycolysis significantly blocks infectious DENV production. This study provides further evidence that viral metabolomic analyses can lead to the discovery of novel therapeutic targets to block the replication of medically important human pathogens. Viruses are obligate intracellular parasites that depend on the metabolic machinery of the host cell to supply the energy and macromolecules necessary for successful replication. In recent years, research has focused on investigating how virus infection alters host metabolism with the hope that these studies will provide insight into the metabolic requirements of viral replication. Viral modulation of the host cell metabolic profile has been examined for several viruses, including human cytomegalovirus (HCMV), herpes simplex virus 1 (HSV-1), hepatitis C virus, influenza A virus, human immunodeficiency virus type 1 (HIV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), vaccinia virus (VACV), and Epstein-Barr virus (1-11). These reports revealed that virus infection triggers dramatic changes in cellular metabolism, particularly in central carbon utilization pathways.Glucose and glutamine represent the two main carbon sources used to support the energetic and biosynthetic needs of mammalian cells. In...

show abstract

Tissue plasminogen activator induced by dengue virus infection of human endothelial cells

Cited by 44 publications

References 29 publications

Interaction of Leptospira interrogans with Human Proteolytic Systems Enhances Dissemination through Endothelial Cells and Protease Levels

Interaction of Leptospira interrogans with Human Proteolytic Systems Enhances Dissemination through Endothelial Cells and Protease Levels

Immunopathogenesis of Dengue Hemorrhagic Fever

Dengue Virus Induces and Requires Glycolysis for Optimal Replication

Contact Info

Product

Resources

About