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Anti-dengue virus nonstructural protein 1 antibodies recognize protein disulfide isomerase on platelets and inhibit platelet aggregation.
Mol Immunol. 2009 Dec; 47(2-3):398-406.MI

Abstract

Hemorrhagic syndrome is a hallmark of severe dengue diseases. We previously suggested a mechanism of molecular mimicry in which antibodies against dengue virus (DV) nonstructural protein 1 (NS1) cross-react with platelets. In the present study, we demonstrate that protein disulfide isomerase (PDI) on the platelet surface is recognized by anti-DV NS1 antibodies. Anti-DV NS1 obtained from hyperimmunized mouse sera inhibited PDI activity and platelet aggregation, and both inhibitory effects were prevented when anti-DV NS1 antibodies were preabsorbed with PDI. Anti-PDI antibodies bound to a peptide consisting of amino acid residues 311-330 (P311-330) of NS1. This peptide was a predicted epitope analyzed by homologous sequence alignments between DV NS1 and PDI. The platelet binding activities of anti-PDI and anti-DV NS1 antibodies were both reduced by P311-330 preabsorption. Similar to the findings using anti-DV NS1, antibodies against P311-330 bound to PDI and platelets, followed by inhibition of PDI activity and platelet aggregation. Furthermore, the cross-reactivity of dengue hemorrhagic fever patient sera with platelets was reduced when patient sera were preabsorbed with PDI or P311-330. Dengue hemorrhagic fever patient sera also inhibited platelet aggregation, while PDI or P311-330 reduced this inhibitory effect. In conclusion, anti-DV NS1 antibodies cross-react with PDI on platelet surface causing inhibition of platelet aggregation, which may provide implications in dengue disease pathogenesis.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Cheng HJ
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
Lei HY
No affiliation info available
Lin CF
No affiliation info available
Luo YH
No affiliation info available
Wan SW
No affiliation info available
Liu HS
No affiliation info available
Yeh TM
No affiliation info available
Lin YS
No affiliation info available

MeSH

AbsorptionAmino Acid SequenceAnimalsAntibodies, ViralBlood PlateletsCell ExtractsCross ReactionsDengue VirusEpitopesHumansMiceMolecular Sequence DataPeptidesPlatelet AggregationProtein Disulfide-IsomerasesSevere DengueViral Nonstructural Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19822367

Citation

Cheng, Hsien-Jen, et al. "Anti-dengue Virus Nonstructural Protein 1 Antibodies Recognize Protein Disulfide Isomerase On Platelets and Inhibit Platelet Aggregation." Molecular Immunology, vol. 47, no. 2-3, 2009, pp. 398-406.
Cheng HJ, Lei HY, Lin CF, et al. Anti-dengue virus nonstructural protein 1 antibodies recognize protein disulfide isomerase on platelets and inhibit platelet aggregation. Mol Immunol. 2009;47(2-3):398-406.
Cheng, H. J., Lei, H. Y., Lin, C. F., Luo, Y. H., Wan, S. W., Liu, H. S., Yeh, T. M., & Lin, Y. S. (2009). Anti-dengue virus nonstructural protein 1 antibodies recognize protein disulfide isomerase on platelets and inhibit platelet aggregation. Molecular Immunology, 47(2-3), 398-406. https://doi.org/10.1016/j.molimm.2009.08.033
Cheng HJ, et al. Anti-dengue Virus Nonstructural Protein 1 Antibodies Recognize Protein Disulfide Isomerase On Platelets and Inhibit Platelet Aggregation. Mol Immunol. 2009;47(2-3):398-406. PubMed PMID: 19822367.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-dengue virus nonstructural protein 1 antibodies recognize protein disulfide isomerase on platelets and inhibit platelet aggregation. AU - Cheng,Hsien-Jen, AU - Lei,Huan-Yao, AU - Lin,Chiou-Feng, AU - Luo,Yueh-Hsia, AU - Wan,Shu-Wen, AU - Liu,Hsiao-Sheng, AU - Yeh,Trai-Ming, AU - Lin,Yee-Shin, Y1 - 2009/10/12/ PY - 2009/06/28/received PY - 2009/08/13/revised PY - 2009/08/28/accepted PY - 2009/10/14/entrez PY - 2009/10/14/pubmed PY - 2009/12/17/medline SP - 398 EP - 406 JF - Molecular immunology JO - Mol Immunol VL - 47 IS - 2-3 N2 - Hemorrhagic syndrome is a hallmark of severe dengue diseases. We previously suggested a mechanism of molecular mimicry in which antibodies against dengue virus (DV) nonstructural protein 1 (NS1) cross-react with platelets. In the present study, we demonstrate that protein disulfide isomerase (PDI) on the platelet surface is recognized by anti-DV NS1 antibodies. Anti-DV NS1 obtained from hyperimmunized mouse sera inhibited PDI activity and platelet aggregation, and both inhibitory effects were prevented when anti-DV NS1 antibodies were preabsorbed with PDI. Anti-PDI antibodies bound to a peptide consisting of amino acid residues 311-330 (P311-330) of NS1. This peptide was a predicted epitope analyzed by homologous sequence alignments between DV NS1 and PDI. The platelet binding activities of anti-PDI and anti-DV NS1 antibodies were both reduced by P311-330 preabsorption. Similar to the findings using anti-DV NS1, antibodies against P311-330 bound to PDI and platelets, followed by inhibition of PDI activity and platelet aggregation. Furthermore, the cross-reactivity of dengue hemorrhagic fever patient sera with platelets was reduced when patient sera were preabsorbed with PDI or P311-330. Dengue hemorrhagic fever patient sera also inhibited platelet aggregation, while PDI or P311-330 reduced this inhibitory effect. In conclusion, anti-DV NS1 antibodies cross-react with PDI on platelet surface causing inhibition of platelet aggregation, which may provide implications in dengue disease pathogenesis. SN - 1872-9142 UR - https://www.unboundmedicine.com/medline/citation/19822367/Anti_dengue_virus_nonstructural_protein_1_antibodies_recognize_protein_disulfide_isomerase_on_platelets_and_inhibit_platelet_aggregation_ DB - PRIME DP - Unbound Medicine ER -