Antibodies from dengue patient sera cross-react with endothelial cells and induce damage.
Dengue virus infection causes a wide range of diseases from the mild febrile illness dengue fever to the life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Vascular leakage and hemorrhagic syndrome are the clinical features associated with dengue infection, yet the mechanisms remain unclear. In this study, the cross-reactivity of dengue patient sera with endothelial cells was demonstrated. There were higher percentages of endothelial cells reactive with dengue hemorrhagic fever/dengue shock syndrome patient sera than those with dengue fever patient sera. The percentages of endothelial cells reactive with patient serum IgM were higher than those with IgG. Further studies showed that the endothelial cell binding activity was inhibited by pretreatment with dengue virus nonstructural protein 1 (NS1). The antibodies against NS1 produced after dengue virus infection may, at least in part, account for the cross-reactivity of patient sera with endothelial cells. Furthermore, dengue patient sera induced endothelial cell apoptosis via a caspase-dependent pathway that was also inhibited by NS1 pretreatment. In addition to apoptosis, patient sera caused cell lysis in the presence of complement, and DHF/DSS patient sera showed higher percentages of cytotoxicity than dengue fever patient sera. Thus, the generation of cross-reactive autoantibodies against endothelial cells would lead to their dysfunction, which may play a role in the pathogenesis of dengue virus infection.
Lin
Chiou-Feng
CF
Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China.
Lei
Huan-Yao
HY
Shiau
Ai-Li
AL
Liu
Ching-Chuan
CC
Liu
Hsiao-Sheng
HS
Yeh
Trai-Ming
TM
Chen
Shun-Hua
SH
Lin
Yee-Shin
YS
D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood*; D018929:Cell Culture Techniques; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M; D019595:Severe Dengue / Q000276:immunology* / Q000821:virology; D017361:Viral Nonstructural Proteins
D000914:Antibodies, Viral; D007075:Immunoglobulin M; C079340:NS1 protein, Dengue virus type 2; D017361:Viral Nonstructural Proteins