Molecular mimicry between virus and host and its implications for dengue disease pathogenesis

Yee Shin Lin, Trai Ming Yeh, Chiou Feng Lin, Shu Wen Wan, Yung Chun Chuang, Tan Kuei Hsu, Hsiao Sheng Liu, Ching Chuan Liu, Robert Anderson, Huan Yao Lei

研究成果: 雜誌貢獻文章

75 引文 斯高帕斯(Scopus)

摘要

Numerous infectious agents may trigger autoimmunity or even result in autoimmune diseases. Several mechanisms have been proposed for pathogen-triggered autoimmunity including molecular mimicry, cryptic antigens, epitope spreading, bystander activation and polyclonal activation. In the case of dengue virus infection which causes serious public health problems, the mechanisms regarding the pathogenesis of dengue hemorrhagic syndrome are not fully resolved. Our previous studiessuggest a mechanism of molecular mimicry in which antibodies directed against dengue virus non-structural protein 1 (NS1) cross-react with human platelets and endothelial cells and cause their damage and dysfunction, which may be related to the clinical features of dengue disease. Several cell surface proteins recognized by patient serum samples and anti-NS1 antibodies have been identified. Based on proteomic studies and sequence analysis, the C-terminal region of dengue virus NS1 shows sequence homology with target proteins. In addition, different regions of dengue virus proteins including core, prM, E and NS1 proteins show sequence homology with different coagulatory molecules. As an example, the amino acid sequence 101-106 of E protein (WGNGCG) shows sequence homology with factors XI, X, IX, VII, II (thrombin), plasminogen and tissue plasminogen activator. Furthermore, single chain variable region against NS1 can interfere with fibrin formation, which leads to prolonged thrombin time. We hypothesize that molecular mimicry between dengue virus proteins and coagulatory molecules may induce cross-reactive autoantibodies that can interfere with coagulation activation. A molecular mimicry pathogenesis for dengue disease which involves cross-reactivity of dengue virus with human endothelial cells, platelets and coagulatory molecules is proposed.

原文英語
頁(從 - 到)515-523
頁數9
期刊Experimental Biology and Medicine
236
發行號5
DOIs
出版狀態已發佈 - 五月 2011
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Lin, Y. S., Yeh, T. M., Lin, C. F., Wan, S. W., Chuang, Y. C., Hsu, T. K., Liu, H. S., Liu, C. C., Anderson, R., & Lei, H. Y. (2011). Molecular mimicry between virus and host and its implications for dengue disease pathogenesis. Experimental Biology and Medicine, 236(5), 515-523. https://doi.org/10.1258/ebm.2011.010339