Dengue virus nonstructural protein NS1 binds to prothrombin/thrombin and inhibits prothrombin activation

Shi Wei Lin, Yung Chun Chuang, Yee-Shin Lin, Huan Yao Lei, Hsiao-Sheng Liu, Trai-Ming Yeh

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Objectives: Dengue virus (DENV) infection may result in severe dengue hemorrhage fever (DHF). However the mechanisms to cause hemorrhage during DENV infection are not fully understood. The sera level of secreted DENV nonstructural protein 1 (NS1) is correlated with the development of DHF. However, whether secreted NS1 can interfere with coagulation and contribute to the hemorrhage in DHF is unknown. Since thrombin plays a very important role in the activation of coagulation, we investigated whether NS1 can bind to thrombin and affect its formation or activity. Methods and results: We first demonstrated that NS1 could bind to thrombin and formed NS1/thrombin complex in dengue patients' sera by enzyme-linked immunosorbent assay (ELISA). The ability of NS1 binding to prothrombin or thrombin was further confirmed using recombinant NS1 (rNS1) by ELISA, co-immunoprecipitation, and rNS1-affinity column purification. Even though the binding of rNS1 to thrombin showed no effect on thrombin activity, rNS1 could inhibit prothrombin activation and prolong activated partial thromboplastin time (APTT) of human platelet poor plasma. Conclusion: These results suggest secreted DENV NS1 may bind to prothrombin and inhibit it activation, which in turn, may contribute to the APTT prolongation and hemorrhage in DHF patients.

Original languageEnglish
Pages (from-to)325-334
Number of pages10
JournalJournal of Infection
Volume64
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1

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Dengue Virus
Prothrombin
Thrombin
Dengue
Hemorrhage
Proteins
Partial Thromboplastin Time
Virus Diseases
Enzyme-Linked Immunosorbent Assay
Severe Dengue
Serum
Immunoprecipitation
Recombinant Proteins
Protein Binding
Blood Platelets

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Lin, Shi Wei ; Chuang, Yung Chun ; Lin, Yee-Shin ; Lei, Huan Yao ; Liu, Hsiao-Sheng ; Yeh, Trai-Ming. / Dengue virus nonstructural protein NS1 binds to prothrombin/thrombin and inhibits prothrombin activation. In: Journal of Infection. 2012 ; Vol. 64, No. 3. pp. 325-334.
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abstract = "Objectives: Dengue virus (DENV) infection may result in severe dengue hemorrhage fever (DHF). However the mechanisms to cause hemorrhage during DENV infection are not fully understood. The sera level of secreted DENV nonstructural protein 1 (NS1) is correlated with the development of DHF. However, whether secreted NS1 can interfere with coagulation and contribute to the hemorrhage in DHF is unknown. Since thrombin plays a very important role in the activation of coagulation, we investigated whether NS1 can bind to thrombin and affect its formation or activity. Methods and results: We first demonstrated that NS1 could bind to thrombin and formed NS1/thrombin complex in dengue patients' sera by enzyme-linked immunosorbent assay (ELISA). The ability of NS1 binding to prothrombin or thrombin was further confirmed using recombinant NS1 (rNS1) by ELISA, co-immunoprecipitation, and rNS1-affinity column purification. Even though the binding of rNS1 to thrombin showed no effect on thrombin activity, rNS1 could inhibit prothrombin activation and prolong activated partial thromboplastin time (APTT) of human platelet poor plasma. Conclusion: These results suggest secreted DENV NS1 may bind to prothrombin and inhibit it activation, which in turn, may contribute to the APTT prolongation and hemorrhage in DHF patients.",
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Dengue virus nonstructural protein NS1 binds to prothrombin/thrombin and inhibits prothrombin activation. / Lin, Shi Wei; Chuang, Yung Chun; Lin, Yee-Shin; Lei, Huan Yao; Liu, Hsiao-Sheng; Yeh, Trai-Ming.

In: Journal of Infection, Vol. 64, No. 3, 01.03.2012, p. 325-334.

Research output: Contribution to journalArticle

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