Rhinovirus-induced VP1-specific Antibodies are Group-specific and Associated With Severity of Respiratory Symptoms

Katarzyna Niespodziana,Clarissa R Cabauatan,David J Jackson,Daniela Gallerano,Belen Trujillo-Torralbo,Ajerico Del Rosario,Patrick Mallia,Rudolf Valenta,Sebastian L Johnston

doi:10.1016/j.ebiom.2014.11.012

Katarzyna Niespodziana, Clarissa R Cabauatan + Show 7 more

Open Access

https://doi.org/10.1016/j.ebiom.2014.11.012

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Abstract

BackgroundRhinoviruses (RVs) are a major cause of common colds and induce exacerbations of asthma and chronic inflammatory lung diseases. MethodsWe expressed and purified recombinant RV coat proteins VP1-4, non-structural proteins as well as N-terminal fragments of VP1 from four RV strains (RV14, 16, 89, C) covering the three known RV groups (RV-A, RV-B and RV-C) and measured specific IgG-subclass-, IgA- and IgM-responses by ELISA in subjects with different severities of asthma or without asthma before and after experimental infection with RV16. FindingsBefore infection subjects showed IgG1>IgA>IgM>IgG3 cross-reactivity with N-terminal fragments from the representative VP1 proteins of the three RV groups. Antibody levels were higher in the asthmatic group as compared to the non-asthmatic subjects. Six weeks after infection with RV16, IgG1 antibodies showed a group-specific increase towards the N-terminal VP1 fragment, but not towards other capsid and non-structural proteins, which was highest in subjects with severe upper and lower respiratory symptoms. InterpretationOur results demonstrate that increases of antibodies towards the VP1 N-terminus are group-specific and associated with severity of respiratory symptoms and suggest that it may be possible to develop serological tests for identifying causative RV groups.

Highlights

Rhinoviruses (RVs) are the most common cause of respiratory illnesses in children and adults of all ages and are responsible for more than 50% of acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD) (Donaldson et al, 2003; Johnston et al, 1995; Nicholson et al, 1993)
Severe RV infections during infancy have been linked to the subsequent development of asthma and the presence of rhinovirus in the lower airway to the Abbreviations: RV, Rhinovirus; COPD, Chronic obstructive pulmonary disease; intercellular adhesion molecule 1 (ICAM-1), Intercellular adhesion molecule 1; low density lipoprotein receptor (LDL-R), Low density lipoprotein receptor; ICS, Inhaled corticosteroids; short acting beta agonists (SABA), Short-acting β2 agonists; peak expiratory flow (PEF), Peak expiratory flow; MALDI–TOF, Matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry; ELISA, Enzyme-linked immunosorbent assay; horseradish peroxidase (HRP), Horseradish peroxidase; O.D, Optical density; human serum albumin (HSA), Human serum albumin; MBP, Maltose binding protein; TCID50, Tissue culture 50% infective dose
Blood samples obtained on the day of RV inoculation showed that the antibody responses of the analysed individuals were mainly directed against a Nterminal fragment of the VP1 protein, whereas the other coat proteins VP2-VP4 as well as the non-structural proteins showed no relevant reactivity

Summary

Introduction

Rhinoviruses (RVs) are the most common cause of respiratory illnesses in children and adults of all ages and are responsible for more than 50% of acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD) (Donaldson et al, 2003; Johnston et al, 1995; Nicholson et al, 1993). Additional support for the causal relationship between RV infections and asthma exacerbations comes from studies in which asthmatic and healthy individuals are subjected to experimental RV infections, in particular using RV16 as a model strain Using such infection studies it has been demonstrated that RV infections increase airway hyperreactivity and late phase asthmatic responses (Lemanske et al, 1989). Methods: We expressed and purified recombinant RV coat proteins VP1-4, non-structural proteins as well as Nterminal fragments of VP1 from four RV strains (RV14, 16, 89, C) covering the three known RV groups (RV-A, RVB and RV-C) and measured specific IgG-subclass-, IgA- and IgM-responses by ELISA in subjects with different severities of asthma or without asthma before and after experimental infection with RV16. Six weeks after infection with RV16, IgG1 antibodies showed a group-specific increase towards the N-terminal VP1 fragment, but not towards other capsid and non-structural proteins, which was highest in subjects with severe upper and lower respiratory symptoms. Interpretation: Our results demonstrate that increases of antibodies towards the VP1 N-terminus are groupspecific and associated with severity of respiratory symptoms and suggest that it may be possible to develop serological tests for identifying causative RV groups

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