Characterization of dengue virus envelope protein.
Date
1997
Authors
He, Runtao.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
Dengue virus infection is the leading cause of morbidity and mortality in many tropical countries. The dengue virus envelope protein (E) plays pivotal roles in mediating infection, pathogenesis and host immune response.
We investigated mechanisms of antibody neutralization of dengue virus infection and found that neutralization occurs mainly by blocking E protein-mediated virus attachment to host cells. Dengue-immune sera demonstrated a strong correlation between cell attachment-blocking and neutralization activities. These activities were correlated with levels of E-specific antibodies and involved IgG rather than IgM.
We found that dengue-specific antibody triggers binding of dengue virus to platelets, which might offer a partial explanation for the thrombocytopenia seen in severe dengue disease. Virus binding was mediated by the E protein and involved a platelet component other than Fc receptor.
Dengue virus E protein was found to form complexes with pre-membrane protein (prM). Previous studies on other flaviviruses suggested that this association is important in virus maturation and release. We found that prM-E association not only forms a heterodimer, but also forms higher order molecular structures. We also presented evidence that the site of prM-E association on E protein is in the carboxy terminal anchoring domain, while cell-binding activity resides in a trypsin-releasable ectodomain of the E protein.
One of the barriers of generating recombinant dengue virus vaccine is to find a low-cost and high level expression eukaryotic system. We, for the first time, expressed dengue virus E protein in yeast, which was used in antibody epitope mapping studies and which represents a potentially attractive vaccine candidate against dengue virus.
Thesis (Ph.D.)--Dalhousie University (Canada), 1997.
We investigated mechanisms of antibody neutralization of dengue virus infection and found that neutralization occurs mainly by blocking E protein-mediated virus attachment to host cells. Dengue-immune sera demonstrated a strong correlation between cell attachment-blocking and neutralization activities. These activities were correlated with levels of E-specific antibodies and involved IgG rather than IgM.
We found that dengue-specific antibody triggers binding of dengue virus to platelets, which might offer a partial explanation for the thrombocytopenia seen in severe dengue disease. Virus binding was mediated by the E protein and involved a platelet component other than Fc receptor.
Dengue virus E protein was found to form complexes with pre-membrane protein (prM). Previous studies on other flaviviruses suggested that this association is important in virus maturation and release. We found that prM-E association not only forms a heterodimer, but also forms higher order molecular structures. We also presented evidence that the site of prM-E association on E protein is in the carboxy terminal anchoring domain, while cell-binding activity resides in a trypsin-releasable ectodomain of the E protein.
One of the barriers of generating recombinant dengue virus vaccine is to find a low-cost and high level expression eukaryotic system. We, for the first time, expressed dengue virus E protein in yeast, which was used in antibody epitope mapping studies and which represents a potentially attractive vaccine candidate against dengue virus.
Thesis (Ph.D.)--Dalhousie University (Canada), 1997.
Keywords
Biology, Microbiology.