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Julien Pompon - One of the best experts on this subject based on the ideXlab platform.

  • dengue virus recruitment of plasmin proteolysis increases mosquito midgut internalization enhancing infection onset and this can be blocked by an endogenous kazal type inhibitor
    Social Science Research Network, 2019
    Co-Authors: Karthik Ramesh, Varsha A. Walvekar, Benjamin Wong, Ahmed Mahmoud Mohammed Sayed, Dorothée Missé, Yu Keung Mok, Manjunatha R Kini, Julien Pompon
    Abstract:

    Deciphering the impact of dengue pathogenesis on vector transmission is critical for understanding virulence evolution, epidemiology and developing transmission-blocking tools. Dengue infection can alter blood coagulation and fibrinolysis pathways, resulting in severe hemorrhage and death. Here, we demonstrate that when plasmin, the human Fibrinolytic Factor, is added to blood meal, it enhances DENV infection in mosquito midgut, resulting in higher dissemination in mosquitoes. In addition, the mosquito midgut-expressed AaTI, a plasmin-selective mosquito Kazal-type inhibitor, reverted this enhanced infection by inhibiting plasmin proteolysis in the midgut lumen. Using bio-layer interferometry, we showed that DENV, plasmin and AaTI interact to form a tripartite complex. Eventually, plasmin supplementation in infectious blood meal increased midgut internalization of dextran molecules and this was reverted by AaTI. Our study demonstrates that: (a) DENV recruits plasmin to increase local proteolytic activity in the midgut, thus degrading the glyocalyx and enhancing DENV infection onset, and (b) AaTI can act as a transmission-blocking agent by inhibiting plasmin proteolysis. Our results indicate that dengue pathogenesis enhances DENV fitness by increasing its infectivity to mosquitoes.

  • Increased Mosquito Midgut Infection by Dengue Virus Recruitment of Plasmin Is Blocked by an Endogenous Kazal-type Inhibitor
    iScience, 2019
    Co-Authors: Karthik Ramesh, Varsha A. Walvekar, Benjamin Wong, Ahmed Mahmoud Mohammed Sayed, Dorothée Missé, R. Manjunatha Kini, Yu Keung Mok, Julien Pompon
    Abstract:

    Dengue symptoms include alteration of blood coagulation and fibrinolysis, causing severe hemorrhage and death. Here, we demonstrate that higher concentration of plasmin, the human Fibrinolytic Factor, in blood meal enhances dengue virus (DENV) infection in mosquito midgut and dissemination in mosquitoes. We also show that mosquitoes express a plasmin-selective Kazal-type inhibitor (AaTI) in the midgut to inhibit plasmin proteolysis and revert the enhanced infection. Using bio-layer interferometry, we show that DENV, plasmin, and AaTI interact to form a tripartite complex. Eventually, plasmin increases midgut internalization of dextran molecules and this is reverted by AaTI. Our study demonstrates that (1) DENV recruits plasmin to increase local proteolytic activity in the midgut, thus degrading the glycocalyx and enhancing DENV internalization and (2) AaTI can act as a transmission-blocking agent by inhibiting plasmin proteolysis. Our results indicate that dengue pathogenesis enhances DENV fitness by increasing its infectivity to mosquitoes.

Ten H Cate - One of the best experts on this subject based on the ideXlab platform.

  • enhancement of rabbit jugular vein thrombolysis by neutralization of Factor xi in vivo evidence for a role of Factor xi as an anti Fibrinolytic Factor
    Journal of Clinical Investigation, 1998
    Co-Authors: M C Minnema, Laurent O Mosnier, Philip W Friederich, Marcel Levi, P A K Von Dem Borne, B J Biemond, C E Hack, B N Bouma, Ten H Cate
    Abstract:

    Recent in vitro studies have shown that Fibrinolytic activity may be attenuated by a thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin, generated via the intrinsic pathway of coagulation in a Factor XI-dependent way. Thus Factor XI may play a role in the regulation of endogenous fibrinolysis. The aim of this study was to investigate the effect of in vivo inhibition of Factor XI and TAFI in an experimental thrombosis model in rabbits. Incorporation of anti-Factor XI antibodies in jugular vein thrombi resulted in an almost twofold increase in endogenous thrombolysis compared with a control antibody. A similar effect was observed when the anti-Factor XI antibody was administered systemically. Inhibition of TAFI activity also resulted in a twofold increase in clot lysis whereas inhibition of both Factor XI and TAFI activity had no additional effect. Thus, we provide the first in vivo evidence for enhanced thrombolysis through inhibition of clotting Factor XI, demonstrating a novel role for the intrinsic pathway of coagulation. Furthermore we demonstrate that inhibition of TAFI had a similar effect on thrombolysis. We postulate that inhibition of Factor XI activity enhances thrombolysis because of diminished indirect activation of TAFI.

Karthik Ramesh - One of the best experts on this subject based on the ideXlab platform.

  • dengue virus recruitment of plasmin proteolysis increases mosquito midgut internalization enhancing infection onset and this can be blocked by an endogenous kazal type inhibitor
    Social Science Research Network, 2019
    Co-Authors: Karthik Ramesh, Varsha A. Walvekar, Benjamin Wong, Ahmed Mahmoud Mohammed Sayed, Dorothée Missé, Yu Keung Mok, Manjunatha R Kini, Julien Pompon
    Abstract:

    Deciphering the impact of dengue pathogenesis on vector transmission is critical for understanding virulence evolution, epidemiology and developing transmission-blocking tools. Dengue infection can alter blood coagulation and fibrinolysis pathways, resulting in severe hemorrhage and death. Here, we demonstrate that when plasmin, the human Fibrinolytic Factor, is added to blood meal, it enhances DENV infection in mosquito midgut, resulting in higher dissemination in mosquitoes. In addition, the mosquito midgut-expressed AaTI, a plasmin-selective mosquito Kazal-type inhibitor, reverted this enhanced infection by inhibiting plasmin proteolysis in the midgut lumen. Using bio-layer interferometry, we showed that DENV, plasmin and AaTI interact to form a tripartite complex. Eventually, plasmin supplementation in infectious blood meal increased midgut internalization of dextran molecules and this was reverted by AaTI. Our study demonstrates that: (a) DENV recruits plasmin to increase local proteolytic activity in the midgut, thus degrading the glyocalyx and enhancing DENV infection onset, and (b) AaTI can act as a transmission-blocking agent by inhibiting plasmin proteolysis. Our results indicate that dengue pathogenesis enhances DENV fitness by increasing its infectivity to mosquitoes.

  • Increased Mosquito Midgut Infection by Dengue Virus Recruitment of Plasmin Is Blocked by an Endogenous Kazal-type Inhibitor
    iScience, 2019
    Co-Authors: Karthik Ramesh, Varsha A. Walvekar, Benjamin Wong, Ahmed Mahmoud Mohammed Sayed, Dorothée Missé, R. Manjunatha Kini, Yu Keung Mok, Julien Pompon
    Abstract:

    Dengue symptoms include alteration of blood coagulation and fibrinolysis, causing severe hemorrhage and death. Here, we demonstrate that higher concentration of plasmin, the human Fibrinolytic Factor, in blood meal enhances dengue virus (DENV) infection in mosquito midgut and dissemination in mosquitoes. We also show that mosquitoes express a plasmin-selective Kazal-type inhibitor (AaTI) in the midgut to inhibit plasmin proteolysis and revert the enhanced infection. Using bio-layer interferometry, we show that DENV, plasmin, and AaTI interact to form a tripartite complex. Eventually, plasmin increases midgut internalization of dextran molecules and this is reverted by AaTI. Our study demonstrates that (1) DENV recruits plasmin to increase local proteolytic activity in the midgut, thus degrading the glycocalyx and enhancing DENV internalization and (2) AaTI can act as a transmission-blocking agent by inhibiting plasmin proteolysis. Our results indicate that dengue pathogenesis enhances DENV fitness by increasing its infectivity to mosquitoes.

M C Minnema - One of the best experts on this subject based on the ideXlab platform.

  • enhancement of rabbit jugular vein thrombolysis by neutralization of Factor xi in vivo evidence for a role of Factor xi as an anti Fibrinolytic Factor
    Journal of Clinical Investigation, 1998
    Co-Authors: M C Minnema, Laurent O Mosnier, Philip W Friederich, Marcel Levi, P A K Von Dem Borne, B J Biemond, C E Hack, B N Bouma, Ten H Cate
    Abstract:

    Recent in vitro studies have shown that Fibrinolytic activity may be attenuated by a thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin, generated via the intrinsic pathway of coagulation in a Factor XI-dependent way. Thus Factor XI may play a role in the regulation of endogenous fibrinolysis. The aim of this study was to investigate the effect of in vivo inhibition of Factor XI and TAFI in an experimental thrombosis model in rabbits. Incorporation of anti-Factor XI antibodies in jugular vein thrombi resulted in an almost twofold increase in endogenous thrombolysis compared with a control antibody. A similar effect was observed when the anti-Factor XI antibody was administered systemically. Inhibition of TAFI activity also resulted in a twofold increase in clot lysis whereas inhibition of both Factor XI and TAFI activity had no additional effect. Thus, we provide the first in vivo evidence for enhanced thrombolysis through inhibition of clotting Factor XI, demonstrating a novel role for the intrinsic pathway of coagulation. Furthermore we demonstrate that inhibition of TAFI had a similar effect on thrombolysis. We postulate that inhibition of Factor XI activity enhances thrombolysis because of diminished indirect activation of TAFI.

Yu Keung Mok - One of the best experts on this subject based on the ideXlab platform.

  • dengue virus recruitment of plasmin proteolysis increases mosquito midgut internalization enhancing infection onset and this can be blocked by an endogenous kazal type inhibitor
    Social Science Research Network, 2019
    Co-Authors: Karthik Ramesh, Varsha A. Walvekar, Benjamin Wong, Ahmed Mahmoud Mohammed Sayed, Dorothée Missé, Yu Keung Mok, Manjunatha R Kini, Julien Pompon
    Abstract:

    Deciphering the impact of dengue pathogenesis on vector transmission is critical for understanding virulence evolution, epidemiology and developing transmission-blocking tools. Dengue infection can alter blood coagulation and fibrinolysis pathways, resulting in severe hemorrhage and death. Here, we demonstrate that when plasmin, the human Fibrinolytic Factor, is added to blood meal, it enhances DENV infection in mosquito midgut, resulting in higher dissemination in mosquitoes. In addition, the mosquito midgut-expressed AaTI, a plasmin-selective mosquito Kazal-type inhibitor, reverted this enhanced infection by inhibiting plasmin proteolysis in the midgut lumen. Using bio-layer interferometry, we showed that DENV, plasmin and AaTI interact to form a tripartite complex. Eventually, plasmin supplementation in infectious blood meal increased midgut internalization of dextran molecules and this was reverted by AaTI. Our study demonstrates that: (a) DENV recruits plasmin to increase local proteolytic activity in the midgut, thus degrading the glyocalyx and enhancing DENV infection onset, and (b) AaTI can act as a transmission-blocking agent by inhibiting plasmin proteolysis. Our results indicate that dengue pathogenesis enhances DENV fitness by increasing its infectivity to mosquitoes.

  • Increased Mosquito Midgut Infection by Dengue Virus Recruitment of Plasmin Is Blocked by an Endogenous Kazal-type Inhibitor
    iScience, 2019
    Co-Authors: Karthik Ramesh, Varsha A. Walvekar, Benjamin Wong, Ahmed Mahmoud Mohammed Sayed, Dorothée Missé, R. Manjunatha Kini, Yu Keung Mok, Julien Pompon
    Abstract:

    Dengue symptoms include alteration of blood coagulation and fibrinolysis, causing severe hemorrhage and death. Here, we demonstrate that higher concentration of plasmin, the human Fibrinolytic Factor, in blood meal enhances dengue virus (DENV) infection in mosquito midgut and dissemination in mosquitoes. We also show that mosquitoes express a plasmin-selective Kazal-type inhibitor (AaTI) in the midgut to inhibit plasmin proteolysis and revert the enhanced infection. Using bio-layer interferometry, we show that DENV, plasmin, and AaTI interact to form a tripartite complex. Eventually, plasmin increases midgut internalization of dextran molecules and this is reverted by AaTI. Our study demonstrates that (1) DENV recruits plasmin to increase local proteolytic activity in the midgut, thus degrading the glycocalyx and enhancing DENV internalization and (2) AaTI can act as a transmission-blocking agent by inhibiting plasmin proteolysis. Our results indicate that dengue pathogenesis enhances DENV fitness by increasing its infectivity to mosquitoes.