TY - JOUR
T1 - Dengue virus nonstructural protein NS1 binds to prothrombin/thrombin and inhibits prothrombin activation
AU - Lin, Shi Wei
AU - Chuang, Yung Chun
AU - Lin, Yee Shin
AU - Lei, Huan Yao
AU - Liu, Hsiao Sheng
AU - Yeh, Trai Ming
PY - 2012/3/1
Y1 - 2012/3/1
N2 - 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.
AB - 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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U2 - 10.1016/j.jinf.2011.11.023
DO - 10.1016/j.jinf.2011.11.023
M3 - Article
C2 - 22138554
AN - SCOPUS:84856605644
VL - 64
SP - 325
EP - 334
JO - Journal of Infection
JF - Journal of Infection
SN - 0163-4453
IS - 3
ER -