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The dengue virus nonstructural-1 protein (NS1) generates antibodies to common epitopes on human blood clotting, integrin/adhesin proteins and binds to human endothelial cells: potential implications in haemorrhagic fever pathogenesis.
Arch Virol. 1997; 142(5):897-916.AV

Abstract

Antibody responses generated by mice to the dengue-2 virus NS1 protein (D-2V NS1) were influenced by MHC class II (I-A) haplotype but each antiserum cross-reacted with human fibrinogen, thrombocytes and endothelial cells. To investigate these findings, a highly avid subclone (MAb 1G5.4-A1-C3) was selected from a parent hybridoma that secreted a monoclonal antibody (MAb) specific for the native dimeric form of D-2V NS1. When MAb reactions were compared using a panel of overlapping synthetic peptides covering the entire protein sequence, dimer specificity was found to be a weak reaction with multiple ELK-type motifs present in either the positive (E/D-hydrophobic-K/R) or negative (K/R-hydrophobic-D/E) orientations. MAb 1G5.4-A1-C3 and highly avid anti-NS1 polyclonal antisera reacted with the NS1 proteins of the four dengue virus serotypes, but only weakly reacted with the NS1 proteins of the other flaviviruses. MAb 1G5.4-A1-C3 and several other anti-NS1 MAbs produced haemorrhage in mice, cross-reacted with human fibrinogen, thrombocytes and endothelial cells, with known epitopes or active sites on human clotting factors and integrin/adhesin proteins present on these cells. D-2V NS1 bound to human endothelial cells via a site within its N-terminal region, which led to significantly increased binding of avid anti-NS1 antibodies. These results identified a potential role of both 'antigenic' and 'biochemical' mimicry in dengue haemorrhagic fever pathogenesis, consistent with clinical data.

Authors+Show Affiliations

Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, U.K.

Pub Type(s)

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

Language

eng

PubMed ID

9191856

Citation

Falconar, A K.. "The Dengue Virus Nonstructural-1 Protein (NS1) Generates Antibodies to Common Epitopes On Human Blood Clotting, Integrin/adhesin Proteins and Binds to Human Endothelial Cells: Potential Implications in Haemorrhagic Fever Pathogenesis." Archives of Virology, vol. 142, no. 5, 1997, pp. 897-916.
Falconar AK. The dengue virus nonstructural-1 protein (NS1) generates antibodies to common epitopes on human blood clotting, integrin/adhesin proteins and binds to human endothelial cells: potential implications in haemorrhagic fever pathogenesis. Arch Virol. 1997;142(5):897-916.
Falconar, A. K. (1997). The dengue virus nonstructural-1 protein (NS1) generates antibodies to common epitopes on human blood clotting, integrin/adhesin proteins and binds to human endothelial cells: potential implications in haemorrhagic fever pathogenesis. Archives of Virology, 142(5), 897-916.
Falconar AK. The Dengue Virus Nonstructural-1 Protein (NS1) Generates Antibodies to Common Epitopes On Human Blood Clotting, Integrin/adhesin Proteins and Binds to Human Endothelial Cells: Potential Implications in Haemorrhagic Fever Pathogenesis. Arch Virol. 1997;142(5):897-916. PubMed PMID: 9191856.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The dengue virus nonstructural-1 protein (NS1) generates antibodies to common epitopes on human blood clotting, integrin/adhesin proteins and binds to human endothelial cells: potential implications in haemorrhagic fever pathogenesis. A1 - Falconar,A K, PY - 1997/1/1/pubmed PY - 1997/1/1/medline PY - 1997/1/1/entrez SP - 897 EP - 916 JF - Archives of virology JO - Arch Virol VL - 142 IS - 5 N2 - Antibody responses generated by mice to the dengue-2 virus NS1 protein (D-2V NS1) were influenced by MHC class II (I-A) haplotype but each antiserum cross-reacted with human fibrinogen, thrombocytes and endothelial cells. To investigate these findings, a highly avid subclone (MAb 1G5.4-A1-C3) was selected from a parent hybridoma that secreted a monoclonal antibody (MAb) specific for the native dimeric form of D-2V NS1. When MAb reactions were compared using a panel of overlapping synthetic peptides covering the entire protein sequence, dimer specificity was found to be a weak reaction with multiple ELK-type motifs present in either the positive (E/D-hydrophobic-K/R) or negative (K/R-hydrophobic-D/E) orientations. MAb 1G5.4-A1-C3 and highly avid anti-NS1 polyclonal antisera reacted with the NS1 proteins of the four dengue virus serotypes, but only weakly reacted with the NS1 proteins of the other flaviviruses. MAb 1G5.4-A1-C3 and several other anti-NS1 MAbs produced haemorrhage in mice, cross-reacted with human fibrinogen, thrombocytes and endothelial cells, with known epitopes or active sites on human clotting factors and integrin/adhesin proteins present on these cells. D-2V NS1 bound to human endothelial cells via a site within its N-terminal region, which led to significantly increased binding of avid anti-NS1 antibodies. These results identified a potential role of both 'antigenic' and 'biochemical' mimicry in dengue haemorrhagic fever pathogenesis, consistent with clinical data. SN - 0304-8608 UR - https://www.unboundmedicine.com/medline/citation/9191856/The_dengue_virus_nonstructural_1_protein__NS1__generates_antibodies_to_common_epitopes_on_human_blood_clotting_integrin/adhesin_proteins_and_binds_to_human_endothelial_cells:_potential_implications_in_haemorrhagic_fever_pathogenesis_ L2 - https://dx.doi.org/10.1007/s007050050127 DB - PRIME DP - Unbound Medicine ER -