The NS1 glycoprotein can generate dramatic antibody-enhanced dengue viral replication in normal out-bred mice resulting in lethal multi-organ disease

Antibody-enhanced replication (AER) of dengue type-2 virus (DENV-2) strains and production of antibody-enhanced disease (AED) was tested in out-bred mice. Polyclonal antibodies (PAbs) generated against the nonstructural-1 (NS1) glycoprotein candidate vaccine of the New Guinea-C (NG-C) or NSx strains...

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Veröffentlicht in:	PloS one 2011-06, Vol.6 (6), p.e21024-e21024
Hauptverfasser:	Falconar, Andrew K I, Martinez, Fernando
Format:	Artikel
Sprache:	eng
Schlagworte:	Alveoli Animals Animals, Outbred Strains Antibodies Antibodies, Monoclonal - immunology Antibodies, Viral - immunology Antibody-Dependent Enhancement - immunology Antigens Antigens, Viral - immunology Apoptosis B cells Biology Brain Cross Reactions - immunology Dengue Dengue fever Dengue hemorrhagic fever Dengue Virus - immunology Dengue Virus - physiology Encephalitis Glycoproteins Haplotypes Health aspects Hepatocytes House mouse Humans Hyperplasia Immunoblotting Immunoglobulin G Immunoglobulins Infections Leukocytes (mononuclear) Lungs Macrophages Megakaryocytes Mice Microglia Microglial cells Multiple Organ Failure - immunology Multiple Organ Failure - virology Mutation Nodules Organ Specificity - immunology Parenchyma Pathogenicity Pathogens Pneumocytes Polyclonal antibodies Pulp Recombination Replication Respiratory distress syndrome Secretion Septum Steatosis Strains (organisms) Studies Thickening Vaccines Vector-borne diseases Viral diseases Viral Nonstructural Proteins - immunology Viral Nonstructural Proteins - isolation & purification Virion - immunology Virions Virology Virus replication Virus Replication - immunology Viruses
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Zusammenfassung:	Antibody-enhanced replication (AER) of dengue type-2 virus (DENV-2) strains and production of antibody-enhanced disease (AED) was tested in out-bred mice. Polyclonal antibodies (PAbs) generated against the nonstructural-1 (NS1) glycoprotein candidate vaccine of the New Guinea-C (NG-C) or NSx strains reacted strongly and weakly with these antigens, respectively. These PAbs contained the IgG2a subclass, which cross-reacted with the virion-associated envelope (E) glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its AER via all mouse Fcγ-receptor classes. Indeed, when these mice were challenged with a low dose (
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0021024