title: Misdirected antibody responses against an N-terminal epitope on human rhinovirus VP1 as explanation for recurrent RV infections.
abstract: Rhinoviruses (RVs) are the primary cause of upper respiratory tract infections, generally known as the common cold. Moreover, RV infections can trigger severe exacerbations of asthma and chronic obstructive pulmonary disease (COPD). We expressed the 4 major RV capsid proteins, VP1-VP4, in Escherichia coli and used these proteins as well as recombinant and synthetic VP1 fragments to study and map antibody responses in RV-infected humans. VP1, which on infection binds to ICAM 1, was identified as a major target for the memory immune response, residing in the IgG1 subclass and IgA class. Interestingly, this response was mainly directed against an N-terminal 20 mer peptide in VP1, P1a, which becomes exposed on intact RV only when it docks to its receptor ICAM 1. Molecular modeling using the 3-dimensional RV capsid structures revealed that P1a was localized inside the capsid and outside the areas involved in receptor binding or RV neutralization. Our results suggest misdirection of antibody responses against a nonprotective epitope as a mechanism how RV escapes immunity and causes recurrent infections. Based on these findings, it may be possible to design vaccines against RV infections and RV-induced respiratory diseases.
authors: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors: Katarzyna
authors: K
authors: Niespodziana
authors: Kamila
authors: K
authors: Napora
authors: Clarissa
authors: C
authors: Cabauatan
authors: Margarete
authors: M
authors: Focke-Tejkl
authors: Walter
authors: W
authors: Keller
authors: Verena
authors: V
authors: Niederberger
authors: Maria
authors: M
authors: Tsolia
authors: Ioannis
authors: I
authors: Christodoulou
authors: Nikolaos G
authors: NG
authors: Papadopoulos
authors: Rudolf
authors: R
authors: Valenta
mesh_terms: D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology*; D002213:Capsid / Q000276:immunology / Q000378:metabolism; D002648:Child; D003139:Common Cold / Q000276:immunology* / Q000821:virology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology; D012229:Rhinovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D012621:Seasons; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014764:Viral Proteins; C074995:viral protein 1, rhinovirus; D018799:Intercellular Adhesion Molecule-1