Antibodies against dengue virus E protein peptide bind to human plasminogen and inhibit plasmin activity

Huang, Yi; Chang, Bi-Ing; Lei, Huan Yao; Liu, H. S.; Liu, C. C.; Wu, Hua; Yeh, Trai Ming

doi:10.1111/j.1365-2249.1997.499-ce1398.x

Cited by 34 publications

(16 citation statements)

References 19 publications

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“…Unlike previous studies that have shown that D4E peptide (E protein aa 100-119) can inhibit binding of dengue patients' Abs to Plg peptide PL + (13,15), ,20% of Ab binding to Plg was inhibited by a synthetic peptide of E protein aa 96-110 (MK peptide) (Fig. 1C).…”

Section: Abs Cross-react To Plg In Denv Patients' and Immunized Mice contrasting

confidence: 74%

“…Autoantibodies against DENV E, NS1, and prM proteins found in DHF/DSS patients can cross-react with different cells such as endothelial cells and platelets, which can lead to cell damage or platelet activation (15,(19)(20)(21)(22). In this study, we found Plg crossreactive Abs in dengue patients from both Kaohsiung (mainly DENV type 2 infection in adult patients) and Vietnam (mainly DENV type 3 in infants).…”

Section: Discussionmentioning

confidence: 50%

“…In our previous studies, using polyclonal Abs purified from the sera of D4E-immunized mice, we found anti-D4E Abs could inhibit Plm activity (15). It is known that, in antiphospholipid syndrome, different mAbs cross-reactive with thrombin could either enhance prothrombin activation or inhibit thrombin activity depending on their specificities (23).…”

Section: Discussionmentioning

confidence: 97%

“…In our previous study, we also demonstrated that D4E peptide can induce Abs against PL + in mice. However, the effect of Plg cross-reactive Abs on Plg activation is still unclear due to the heterogeneity of Abs in mouse antisera (15). In this study, we generated mAbs against DENV and identified a mAb, 6H11, that can cross-react with Plg.…”

Section: Engue Virus (Denv) Infection Is the Most Importantmentioning

confidence: 99%

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Dengue Virus-Induced Autoantibodies Bind to Plasminogen and Enhance Its Activation

Chuang

Lei

Lin

et al. 2011

The Journal of Immunology

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Dengue virus infection can lead to life-threatening dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in patients. Abnormal activation of the coagulation and fibrinolysis system is one of the hallmarks associated with DHF/DSS patients. However, the mechanisms that cause pathology in DHF/DSS patients are still unclear. Because conversion of plasminogen (Plg) to plasmin (Plm) is the first step in the activation of fibrinolysis, Abs against Plg found in DHF/DSS patients may be important. Therefore, to investigate the specificity, function, and possible origin of these Abs, we generated several Plg cross-reactive mAbs from DENV-immunized mice. An IgG mAb, 6H11, which recognizes an epitope associated with a dengue envelope protein, demonstrated a high level of cross-reactivity with Plg. The 6H11 Ab was further characterized with regard to its effect on Plg activation. Using Plm-specific chromogenic substrate S-2251, we found that mAb 6H11 demonstrated serine protease activity and could convert Plg directly to Plm. The serine protease activity of mAb 6H11 was further confirmed using serine protease chromogenic substrate S-2288. In addition, we found several Plg cross-reactive mAbs that could enhance urokinase-induced Plg activation. Lastly, mAb 6H11 could induce Plm activity and increase the level of D-dimer (a fibrin degradation product) in both human and mouse platelet-poor plasma. Taken together, these data suggest DENV-induced Plg cross-reactive Abs may enhance Plg conversion to Plm, which would be expected to contribute to hyperfibrinolysis in DHF/DSS patients.

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Section: Abs Cross-react To Plg In Denv Patients' and Immunized Mice contrasting

confidence: 74%

Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 97%

Section: Engue Virus (Denv) Infection Is the Most Importantmentioning

confidence: 99%

See 2 more Smart Citations

Dengue Virus-Induced Autoantibodies Bind to Plasminogen and Enhance Its Activation

Chuang

Lei

Lin

et al. 2011

The Journal of Immunology

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“…Monoclonal anti-NS1 antibodies were reported to cross-react with thrombocytes, endothelial cells and human clotting factors, such as fibrinogen [10] . In addition, anti-E antibodies were also reported to bind to plasminogen and inhibit plasmin activity [19][20][21] . In this study, we demonstrated that except anti-NS1and anti-E antibodies, anti-prM antibody could be an autoantibody and may cross-react with epithelial cells, kidney cells, endothelial cells and even T lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Anti-prM Antibody as an Autoantibody in Dengue Virus Infection

Huang¹,

Cheng²,

Lin³

et al. 2008

American J. of Infectious Diseases

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Abstract:We have reported that anti-prM antibody is an enhancing antibody that enhances DV infection of non-Fc receptor bearing cells by dual specificity. We identified the epitope recognized by this anti-prM antibody, M3, which is located at the a.a.53-67of the prM protein nearby the prM/M cleavage junction and these anti-M3 antibodies could be detected in dengue patients sera. Surprisingly, this anti-prM antibody not only recognizes the prM protein of dengue virions, but also cross-reacts with epithelial cells, endothelial cells as well as T cells. The binding of anti-prM antibody to endothelial cells was dose-dependent and could be blocked by M3 peptides. Human M3-specific antibodies from dengue patient sera were demonstrated to be able to bind to endothelial cells and mediate ADE infection on K562 cells. Furthermore, the anti-prM antibody will mediate the antibodydependent cell phagocytosis, leading to the similar severe form of DHF/DSS. In conclusion, anti-prM antibody plays two roles in the pathogenesis of dengue virus infection: to be an enhancing antibody and an autoantibody as well.

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Activation of coagulation and fibrinolysis during dengue virus infection

et al. 2001

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Dengue virus infection can induce mild dengue fever (DF) or severe dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in human. The pathogenesis of hemorrhage in dengue virus infection is not fully understood. Since hemostasis depends on the balance between coagulation and fibrinolysis, alternation of some coagulation parameters (platelet count and activated partial thromoboplastin time, APTT) as well as fibrinolytic parameters (tissue plasminogen activator, tPA and plasminogen activator inhibitor-1, PAI-1) were compared in 8 DHF/DSS and 17 DF patients. Patients showed thrombocytopenia, APTT prolongation, and tPA increase in the acute stage of disease, indicating activation of coagulation and fibrinolysis. The activation of coagulation and fibrinolysis in DHF/DSS patients was much more severe than DF patients. In the convalescent stage, a rise of PAI-1 level and platelet count with concomitant decline of tPA level and APTT returned to normal in both DHF/DSS and DF patients. Therefore, the activation of coagulation and fibrinolysis during the acute stage of dengue virus infection is offset by the increase of platelet and PAI-1 during convalescent stage. Taken together, these results suggest that the degree of coagulation and fibrinolysis activation induced by dengue virus infection is associated with the disease severity.

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Antibodies against dengue virus E protein peptide bind to human plasminogen and inhibit plasmin activity

Cited by 34 publications

References 19 publications

Dengue Virus-Induced Autoantibodies Bind to Plasminogen and Enhance Its Activation

Dengue Virus-Induced Autoantibodies Bind to Plasminogen and Enhance Its Activation

Anti-prM Antibody as an Autoantibody in Dengue Virus Infection

Activation of coagulation and fibrinolysis during dengue virus infection

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