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

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)515-523
Number of pages9
JournalExperimental Biology and Medicine
Volume236
Issue number5
DOIs
Publication statusPublished - May 2011
Externally publishedYes

Fingerprint

Molecular Mimicry
Dengue
Dengue Virus
Viruses
Proteins
Viral Structural Proteins
Sequence Homology
Autoimmunity
Chemical activation
Blood Platelets
Endothelial Cells
Endothelial cells
Factor XI
Platelets
Thrombin
Severe Dengue
Thrombin Time
Amino Acid Sequence Homology
Molecules
Antibodies

Keywords

  • Autoimmunity
  • Coagulatory molecules
  • Dengue virus
  • Endothelial cells
  • Molecular mimicry
  • Platelets

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Molecular mimicry between virus and host and its implications for dengue disease pathogenesis. / Lin, Yee Shin; Yeh, Trai Ming; Lin, Chiou Feng; Wan, Shu Wen; Chuang, Yung Chun; Hsu, Tan Kuei; Liu, Hsiao Sheng; Liu, Ching Chuan; Anderson, Robert; Lei, Huan Yao.

In: Experimental Biology and Medicine, Vol. 236, No. 5, 05.2011, p. 515-523.

Research output: Contribution to journalArticle

Lin, YS, Yeh, TM, Lin, CF, Wan, SW, Chuang, YC, Hsu, TK, Liu, HS, Liu, CC, Anderson, R & Lei, HY 2011, 'Molecular mimicry between virus and host and its implications for dengue disease pathogenesis', Experimental Biology and Medicine, vol. 236, no. 5, pp. 515-523. https://doi.org/10.1258/ebm.2011.010339
Lin, Yee Shin ; Yeh, Trai Ming ; Lin, Chiou Feng ; Wan, Shu Wen ; Chuang, Yung Chun ; Hsu, Tan Kuei ; Liu, Hsiao Sheng ; Liu, Ching Chuan ; Anderson, Robert ; Lei, Huan Yao. / Molecular mimicry between virus and host and its implications for dengue disease pathogenesis. In: Experimental Biology and Medicine. 2011 ; Vol. 236, No. 5. pp. 515-523.
@article{918ba4a998254bd9af8cdd0493e9e60f,
title = "Molecular mimicry between virus and host and its implications for dengue disease pathogenesis",
abstract = "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.",
keywords = "Autoimmunity, Coagulatory molecules, Dengue virus, Endothelial cells, Molecular mimicry, Platelets",
author = "Lin, {Yee Shin} and Yeh, {Trai Ming} and Lin, {Chiou Feng} and Wan, {Shu Wen} and Chuang, {Yung Chun} and Hsu, {Tan Kuei} and Liu, {Hsiao Sheng} and Liu, {Ching Chuan} and Robert Anderson and Lei, {Huan Yao}",
year = "2011",
month = "5",
doi = "10.1258/ebm.2011.010339",
language = "English",
volume = "236",
pages = "515--523",
journal = "Experimental Biology and Medicine",
issn = "1535-3702",
publisher = "SAGE Publications Ltd",
number = "5",

}

TY - JOUR

T1 - Molecular mimicry between virus and host and its implications for dengue disease pathogenesis

AU - Lin, Yee Shin

AU - Yeh, Trai Ming

AU - Lin, Chiou Feng

AU - Wan, Shu Wen

AU - Chuang, Yung Chun

AU - Hsu, Tan Kuei

AU - Liu, Hsiao Sheng

AU - Liu, Ching Chuan

AU - Anderson, Robert

AU - Lei, Huan Yao

PY - 2011/5

Y1 - 2011/5

N2 - 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.

AB - 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.

KW - Autoimmunity

KW - Coagulatory molecules

KW - Dengue virus

KW - Endothelial cells

KW - Molecular mimicry

KW - Platelets

UR - http://www.scopus.com/inward/record.url?scp=79958853212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958853212&partnerID=8YFLogxK

U2 - 10.1258/ebm.2011.010339

DO - 10.1258/ebm.2011.010339

M3 - Article

C2 - 21502191

AN - SCOPUS:79958853212

VL - 236

SP - 515

EP - 523

JO - Experimental Biology and Medicine

JF - Experimental Biology and Medicine

SN - 1535-3702

IS - 5

ER -