Pan-Viral Screening of Respiratory Tract Infections in Adults With and Without Asthma Reveals Unexpected Human Coronavirus and Human Rhinovirus Diversity

Abstract Background. Between 50% and 80% of asthma exacerbations are associated with viral respiratory tract infections (RTIs), yet the influence of viral pathogen diversity on asthma outcomes is poorly understood because of the limited scope and throughput of conventional viral detection methods. Methods. We investigated the capability of the Virochip, a DNA microarray—based viral detection platform, to characterize viral diversity in RTIs in adults with and without asthma. Results. The Virochip detected viruses in a higher proportion of samples (65%) than did culture isolation (17%) while exhibiting high concordance (98%) with and comparable sensitivity (97%) and specificity (98%) to pathogen-specific polymerase chain reaction. A similar spectrum of viruses was identified in the RTIs of each patient subgroup; however, unexpected diversity among human coronaviruses (HCoVs) and human rhinoviruses (HRVs) was revealed. All but one of the HCoVs corresponded to the newly recognized HCoV-NL63 and HCoV-HKU1 viruses, and >20 different serotypes of HRVs were detected, including a set of 5 divergent isolates that formed a distinct genetic subgroup. Conclusions. The Virochip can detect both known and novel variants of viral pathogens present in RTIs. Given the diversity detected here, larger-scale studies will be necessary to determine whether particular substrains of viruses confer an elevated risk of asthma exacerbation.

[1]  Ash A. Alizadeh,et al.  Diagnosis of a Critical Respiratory Illness Caused by Human Metapneumovirus by Use of a Pan-Virus Microarray , 2007, Journal of Clinical Microbiology.

[2]  L. Shackelton,et al.  Characterisation of a newly identified human rhinovirus, HRV-QPM, discovered in infants with bronchiolitis , 2007, Journal of Clinical Virology.

[3]  E. Mardis,et al.  Genome-wide diversity and selective pressure in the human rhinovirus , 2007, Virology Journal.

[4]  G. Palacios,et al.  MassTag Polymerase-Chain-Reaction Detection of Respiratory Pathogens, Including a New Rhinovirus Genotype, That Caused Influenza-Like Illness in New York State during 2004–2005 , 2006, The Journal of infectious diseases.

[5]  Joseph L. DeRisi,et al.  Microarray Detection of Human Parainfluenzavirus 4 Infection Associated with Respiratory Failure in an Immunocompetent Adult , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  B. Berkhout,et al.  Human coronavirus NL63, a new respiratory virus , 2006, FEMS microbiology reviews.

[7]  J. Kahn,et al.  Coronavirus HKU1 Infection in the United States , 2006, Emerging infectious diseases.

[8]  J. Derisi,et al.  Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant , 2006, PLoS pathogens.

[9]  H. Goossens,et al.  Detection of Rhinoviruses by Tissue Culture and Two Independent Amplification Techniques, Nucleic Acid Sequence-Based Amplification and Reverse Transcription-PCR, in Children with Acute Respiratory Infections during a Winter Season , 2006, Journal of Clinical Microbiology.

[10]  A. B. Kay,et al.  The role of T lymphocytes in asthma. , 2006, Chemical immunology and allergy.

[11]  Joseph L DeRisi,et al.  E-Predict: a computational strategy for species identification based on observed DNA microarray hybridization patterns , 2005, Genome Biology.

[12]  Roger L. Brown,et al.  The Wisconsin Upper Respiratory Symptom Survey is responsive, reliable, and valid , 2005, Journal of Clinical Epidemiology.

[13]  Samson S. Y. Wong,et al.  Characterization and Complete Genome Sequence of a Novel Coronavirus, Coronavirus HKU1, from Patients with Pneumonia , 2005, Journal of Virology.

[14]  W. Tan.  Viruses in asthma exacerbations , 2005, Current opinion in pulmonary medicine.

[15]  M. P. Cummings.  PHYLIP (Phylogeny Inference Package) , 2004 .

[16]  F. Hayden.  Rhinovirus and the lower respiratory tract† , 2004, Reviews in medical virology.

[17]  James M. Eldred,et al.  Viral Discovery and Sequence Recovery Using DNA Microarrays , 2003, PLoS biology.

[18]  J. Derisi,et al.  Microarray-based detection and genotyping of viral pathogens , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[19]  S. Johnston,et al.  Viruses in asthma , 2002, British medical bulletin.

[20]  S. Blomqvist,et al.  Genetic clustering of all 102 human rhinovirus prototype strains: serotype 87 is close to human enterovirus 70. , 2002, The Journal of general virology.

[21]  W. Busse,et al.  Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection. , 2000, American journal of respiratory and critical care medicine.

[22]  S. Johnston,et al.  Peak expiratory flow changes during experimental rhinovirus infection. , 2000, The European respiratory journal.

[23]  E. D. de KLERK,et al.  Experimental rhinovirus 16 infection causes variable airway obstruction in subjects with atopic asthma. , 1999, American journal of respiratory and critical care medicine.

[24]  H. Boushey,et al.  Rhinovirus-16 colds in healthy and in asthmatic subjects: similar changes in upper and lower airways. , 1999, American journal of respiratory and critical care medicine.

[25]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[26]  P. Green,et al.  Consed: a graphical tool for sequence finishing. , 1998, Genome research.

[27]  H. Teichtahl,et al.  The Incidence of Respiratory Tract Infection in Adults Requiring Hospitalization for Asthma , 1997, Chest.

[28]  E. D. de KLERK,et al.  Experimental rhinovirus 16 infection. Effects on cell differentials and soluble markers in sputum in asthmatic subjects. , 1997, American journal of respiratory and critical care medicine.

[29]  E. D. de KLERK,et al.  Effects of experimental rhinovirus 16 infection on airway hyperresponsiveness to bradykinin in asthmatic subjects in vivo. , 1997, American journal of respiratory and critical care medicine.

[30]  E. D. de KLERK,et al.  Effect of experimental rhinovirus 16 colds on airway hyperresponsiveness to histamine and interleukin‐8 in nasal lavage in asthmatic subjects in vivo , 1997, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[31]  W. Doyle,et al.  Prechallenge Antibodies: Moderators of Infection Rate, Signs, and Symptoms in Adults Experimentally Challenged With Rhinovirus Type 39 , 1996, The Laryngoscope.

[32]  M J Campbell,et al.  The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis. , 1996, American journal of respiratory and critical care medicine.

[33]  E. D. de KLERK,et al.  Rhinovirus inhalation causes long-lasting excessive airway narrowing in response to methacholine in asthmatic subjects in vivo. , 1995, American journal of respiratory and critical care medicine.

[34]  Stephen T Holgate,et al.  Community study of role of viral infections in exacerbations of asthma in 9-11 year old children , 1995, BMJ.

[35]  S. Johnston,et al.  Lower airways inflammation during rhinovirus colds in normal and in asthmatic subjects. , 1995, American journal of respiratory and critical care medicine.

[36]  K. Nicholson,et al.  Respiratory viruses and exacerbations of asthma in adults. , 1993, BMJ.

[37]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[38]  P. Lewi,et al.  Two groups of rhinoviruses revealed by a panel of antiviral compounds present sequence divergence and differential pathogenicity , 1990, Journal of virology.

[39]  P. Suratt,et al.  Exacerbations of asthma in adults during experimental rhinovirus infection. , 1985, The American review of respiratory disease.

[40]  R. Colonno,et al.  Many rhinovirus serotypes share the same cellular receptor , 1984, Journal of virology.

[41]  J. Fox,et al.  Antigenic groupings of 90 rhinovirus serotypes , 1982, Infection and immunity.

[42]  C. Ellenbogen.  The common cold. , 1981, American family physician.

[43]  J. Hendley,et al.  Coronavirus infections in working adults. Eight-year study with 229 E and OC 43. , 1972, The American review of respiratory disease.