Study on the pathological effects of anti-dengue virus nonstructural protein 1 antibodies in the animal model

• Main Authors: Chu-Chen Cheng, 鄭曲真
• Other Authors: Yee- Shin Lin
• Format: Others
• Language: zh-TW
• Published: 2001
• Online Access: http://ndltd.ncl.edu.tw/handle/66293352921097144878

碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 90 === Dengue viruses (DV; serotypes 1 to 4) belonging to the Flaviviridae are mosquito-born virus. Patients with dengue virus infection show a wide range of clinical effects, from mild fever to life-threatening symptoms of hemorrhagic fever and/or shock syndrome (DHF/DSS). Elevation of liver enzymes including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) could be observed in dengue virus-infected patients. In previous studies, the anti-dengue virus nonstructural protein 1 (NS1) antibodies present in patient and immune murine sera were detected, and their reactivities with endothelial cells and platelets were demonstrated. For the safety concern of vaccine development, whether anti-NS1 antibodies may cause harmful effects, such as increase in vascular permeability, and hepatic and renal injury, are of interest for investigation. C3H/HeN mice were immunized with recombinant DV NS1 or Japanese encephalitis virus (JEV) NS1 as a control for one, three, or five times, and the anti-NS1 IgG and IgM were determined. High titers of anti-NS1 IgG were detected after injection with NS1 for 3 or 5 times. Anti-NS1 IgM could also be detected with a highest level after 5-time injection of NS1. Elevated levels of liver enzymes, especially the AST, could be detected in DV NS1 hyper-immune sera as compared to JEV NS1 hyper-immune sera, but the change of BUN was not observed. Gross and histological examination of NS1 hyper-immunized C3H/HeN mice revealed tissue damage in livers, especially in mice which had higher AST, but all histological examination of kidneys appeared normal without evidence of pathology. Moreover, in dengue pathology, the vascular leakage is one of the clinical features associated with DHF/DSS. Using subcutaneous injection of anti-NS1 antibodies into BALB/c mice, the anti-NS1 antibodies caused an increase in the permeability of mouse vessel in vivo. Taken together, studies in the animal model of this project indicated that the generation of anti-NS1 antibodies may play a role in the pathogenesis of dengue virus infection.