Advertisement

Rhinoviruses and Their Receptors: Implications for Allergic Disease

  • Yury A. BochkovEmail author
  • James E. Gern
Allergens (RK Bush and JA Woodfolk, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Allergens

Abstract

Human rhinoviruses (RVs) are picornaviruses that can cause a variety of illnesses including the common cold, lower respiratory tract illnesses such as bronchitis and pneumonia, and exacerbations of asthma. RVs are classified into three species, RV-A, B, and C, which include over 160 types. They utilize three major types of cellular membrane glycoproteins to gain entry into the host cell: intercellular adhesion molecule 1 (ICAM-1) (the majority of RV-A and all RV-B), low-density lipoprotein receptor (LDLR) family members (12 RV-A types), and cadherin-related family member 3 (CDHR3) (RV-C). CDHR3 is a member of cadherin superfamily of transmembrane proteins with yet unknown biological function, and there is relatively little information available about the mechanisms of RV-C interaction with CDHR3. A coding single nucleotide polymorphism (rs6967330) in CDHR3 could promote RV-C infections and illnesses in infancy, which could in turn adversely affect the developing lung to increase the risk of asthma. Further studies are needed to determine how RV infections contribute to pathogenesis of asthma and to develop the optimal treatment approach to control asthma exacerbations.

Keywords

Human rhinovirus Cellular receptor ICAM-1 LDLR CDHR3 Asthma Allergy 

Notes

Acknowledgments

This work was supported by the following NIH grants: UM1 AI114271, U19 AI104317, and P01 HL070831.

Compliance with Ethical Standards

Conflict of Interest

Dr. Bochkov declares no conflict of interest. Dr. Gern has served as a consultant to PREP Biopharm Inc., Janssen, and Regeneron and has received a lecture honorarium from Boehringer Ingelheim.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Hamparian VV, Colonno RJ, Cooney MK, et al. A collaborative report: rhinoviruses—extension of the numbering system from 89 to 100. Virology. 1987;159:191–2.PubMedCrossRefGoogle Scholar
  2. 2.
    McIntyre CL, Knowles NJ, Simmonds P. Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types. J Gen Virol. 2013;94:1791–806.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Lamson D, Renwick N, Kapoor V, 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. J Infect Dis. 2006;194:1398–402.PubMedCrossRefGoogle Scholar
  4. 4.
    Arden KE, McErlean P, Nissen MD, et al. Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections. J Med Virol. 2006;78:1232–40.PubMedCrossRefGoogle Scholar
  5. 5.
    Lau SK, Yip CC, Tsoi HW, et al. Clinical features and complete genome characterization of a distinct human rhinovirus (HRV) genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children. J Clin Microbiol. 2007;45:3655–64.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Arden KE, Mackay IM. Newly identified human rhinoviruses: molecular methods heat up the cold viruses. Rev Med Virol. 2010;20:156–76.PubMedCrossRefGoogle Scholar
  7. 7.
    Arden KE, Faux CE, O'Neill NT, et al. Molecular characterization and distinguishing features of a novel human rhinovirus (HRV) C, HRVC-QCE, detected in children with fever, cough and wheeze during 2003. J Clin Virol. 2010;47:219–23.PubMedCrossRefGoogle Scholar
  8. 8.
    Bochkov YA, Palmenberg AC, Lee WM, et al. Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. Nat Med. 2011;17:627–32.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Simmonds P, McIntyre C, Savolainen-Kopra C, et al. Proposals for the classification of human rhinovirus species C into genotypically assigned types. J Gen Virol. 2010;91:2409–19.PubMedCrossRefGoogle Scholar
  10. 10.
    Gern JE, Busse WW. Association of rhinovirus infections with asthma. Clin Microbiol Rev. 1999;12:9–18.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Hayden FG. Rhinovirus and the lower respiratory tract. Rev Med Virol. 2004;14:17–31.PubMedCrossRefGoogle Scholar
  12. 12.
    McManus TE, Marley AM, Baxter N, et al. Respiratory viral infection in exacerbations of COPD. Respir Med. 2008;102:1575–80.PubMedCrossRefGoogle Scholar
  13. 13.
    Gern JE. The ABCs of rhinoviruses, wheezing, and asthma. J Virol. 2010;84:7418–26.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Jackson DJ, Gangnon RE, Evans MD, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med. 2008;178:667–72.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Jackson DJ, Lemanske RF, Jr. The role of respiratory virus infections in childhood asthma inception. Immunol Allergy Clin North Am 2010; 30:513–22, vi.Google Scholar
  16. 16.
    van der Gugten AC, van der Zalm MM, Uiterwaal CS, et al. Human rhinovirus and wheezing: short and long-term associations in children. Pediatr Infect Dis J. 2013;32:827–33.PubMedGoogle Scholar
  17. 17.
    Piralla A, Rovida F, Campanini G, et al. Clinical severity and molecular typing of human rhinovirus C strains during a fall outbreak affecting hospitalized patients. J Clin Virol. 2009;45:311–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Han TH, Chung JY, Hwang ES, Koo JW. Detection of human rhinovirus C in children with acute lower respiratory tract infections in South Korea. Arch Virol. 2009;154:987–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Arden KE, Chang AB, Lambert SB, et al. Newly identified respiratory viruses in children with asthma exacerbation not requiring admission to hospital. J Med Virol. 2010;82:1458–61.PubMedCrossRefGoogle Scholar
  20. 20.
    Xiang Z, Gonzalez R, Wang Z, et al. Human rhinoviruses in Chinese adults with acute respiratory tract infection. J Infect. 2010;61:289–98.PubMedCrossRefGoogle Scholar
  21. 21.
    Bizzintino J, Lee WM, Laing IA, et al. Association between human rhinovirus C and severity of acute asthma in children. Eur Respir J. 2011;37:1037–42.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Moreira LP, Kamikawa J, Watanabe AS, et al. Frequency of human rhinovirus species in outpatient children with acute respiratory infections at primary care level in Brazil. Pediatr Infect Dis J. 2011;30:612–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Piralla A, Baldanti F, Gerna G. Phylogenetic patterns of human respiratory picornavirus species, including the newly identified group C rhinoviruses, during a 1-year surveillance of a hospitalized patient population in Italy. J Clin Microbiol. 2011;49:373–6.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Lee WM, Lemanske Jr RF, Evans MD, et al. Human rhinovirus species and season of infection determine illness severity. Am J Respir Crit Care Med. 2012;186:886–91.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Fawkner-Corbett DW, Khoo SK, Duarte MC, et al. Rhinovirus-C detection in children presenting with acute respiratory infection to hospital in Brazil. J Med Virol 2015Google Scholar
  26. 26.
    Uncapher CR, DeWitt CM, Colonno RJ. The major and minor group receptor families contain all but one human rhinovirus serotype. Virology. 1991;180:814–7.PubMedCrossRefGoogle Scholar
  27. 27.••
    Bochkov YA, Watters K, Ashraf S, et al. Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication. Proc Natl Acad Sci U S A. 2015;112:5485–90. Identifies the first cellular factor, CDHR3, mediating RV-C entry into host cells, and reports the development of the first transduced HeLa-E8 cell line for RV-C propagation. Data suggest that rs6967330 single nucleotide polymorphism in CDHR3 could be a risk factor for RV-C wheezing illnesses.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Hao W, Bernard K, Patel N, et al. Infection and propagation of human rhinovirus C in human airway epithelial cells. J Virol. 2012;86:13524–32.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Ashraf S, Brockman-Schneider R, Bochkov YA, et al. Biological characteristics and propagation of human rhinovirus-C in differentiated sinus epithelial cells. Virology. 2013;436:143–9.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Tapparel C, Sobo K, Constant S, et al. Growth and characterization of different human rhinovirus C types in three-dimensional human airway epithelia reconstituted in vitro. Virology. 2013;446:1–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Ashraf S, Brockman-Schneider R, Gern JE. Propagation of rhinovirus-C strains in human airway epithelial cells differentiated at air-liquid interface. Methods Mol Biol. 2015;1221:63–70.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Gavala ML, Bertics PJ, Gern JE. Rhinoviruses, allergic inflammation, and asthma. Immunol Rev. 2011;242:69–90.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Cheung DS, Grayson MH. Role of viruses in the development of atopic disease in pediatric patients. Curr Allergy Asthma Rep. 2012;12:613–20.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Gavala ML, Bashir H, Gern JE. Virus/allergen interactions in asthma. Curr Allergy Asthma Rep. 2013;13:298–307.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Rowe RK, Gill MA. Asthma: the interplay between viral infections and allergic diseases. Immunol Allergy Clin North Am. 2015;35:115–27.PubMedCrossRefGoogle Scholar
  36. 36.
    Tam JS, Jackson WT, Hunter D, et al. Rhinovirus specific IgE can be detected in human sera. J Allergy Clin Immunol. 2013;132:1241–3.PubMedCrossRefGoogle Scholar
  37. 37.
    Pitkaranta A, Arruda E, Malmberg H, Hayden FG. Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR. J Clin Microbiol. 1997;35:1791–3.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Pitkaranta A, Starck M, Savolainen S, et al. Rhinovirus RNA in the maxillary sinus epithelium of adult patients with acute sinusitis. Clin Infect Dis. 2001;33:909–11.PubMedCrossRefGoogle Scholar
  39. 39.
    Pitkaranta A, Puhakka T, Makela MJ, et al. Detection of rhinovirus RNA in middle turbinate of patients with common colds by in situ hybridization. J Med Virol. 2003;70:319–23.PubMedCrossRefGoogle Scholar
  40. 40.
    Mosser AG, Vrtis R, Burchell L, et al. Quantitative and qualitative analysis of rhinovirus infection in bronchial tissues. Am J Respir Crit Care Med. 2005;171:645–51.PubMedCrossRefGoogle Scholar
  41. 41.
    Chantzi FM, Papadopoulos NG, Bairamis T, et al. Human rhinoviruses in otitis media with effusion. Pediatr Allergy Immunol. 2006;17:514–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Malmstrom K, Pitkaranta A, Carpen O, et al. Human rhinovirus in bronchial epithelium of infants with recurrent respiratory symptoms. J Allergy Clin Immunol. 2006;118:591–6.PubMedCrossRefGoogle Scholar
  43. 43.
    D'Amato G, Holgate ST, Pawankar R, et al. Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization. World Allergy Organ J. 2015;8:25.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Gelfand EW. Pediatric asthma: a different disease. Proc Am Thorac Soc. 2009;6:278–82.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Gaffin JM, Kanchongkittiphon W, Phipatanakul W. Perinatal and early childhood environmental factors influencing allergic asthma immunopathogenesis. Int Immunopharmacol. 2014;22:21–30.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Schatz M, Rosenwasser L. The allergic asthma phenotype. J Allergy Clin Immunol Pract. 2014;2:645–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Dougherty RH, Fahy JV. Acute exacerbations of asthma: epidemiology, biology and the exacerbation-prone phenotype. Clin Exp Allergy. 2009;39:193–202.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Doherty GJ, McMahon HT. Mechanisms of endocytosis. Annu Rev Biochem. 2009;78:857–902.PubMedCrossRefGoogle Scholar
  49. 49.
    Fuchs R, Blaas D. Uncoating of human rhinoviruses. Rev Med Virol. 2010;20:281–97.PubMedCrossRefGoogle Scholar
  50. 50.•
    Fuchs R, Blaas D. Productive entry pathways of human rhinoviruses. Adv Virol. Adv Virol 2012;2012:826301. A detailed review on the RV-A and RV-B receptors and mechanisms of viral entry into host cells.Google Scholar
  51. 51.
    Grunert HP, Wolf KU, Langner KD, et al. Internalization of human rhinovirus 14 into HeLa and ICAM-1-transfected BHK cells. Med Microbiol Immunol. 1997;186:1–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Snyers L, Zwickl H, Blaas D. Human rhinovirus type 2 is internalized by clathrin-mediated endocytosis. J Virol. 2003;77:5360–9.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Bayer N, Schober D, Huttinger M, et al. Inhibition of clathrin-dependent endocytosis has multiple effects on human rhinovirus serotype 2 cell entry. J Biol Chem. 2001;276:3952–62.PubMedCrossRefGoogle Scholar
  54. 54.
    Vlasak M, Goesler I, Blaas D. Human rhinovirus type 89 variants use heparan sulfate proteoglycan for cell attachment. J Virol. 2005;79:5963–70.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Khan AG, Pichler J, Rosemann A, Blaas D. Human rhinovirus type 54 infection via heparan sulfate is less efficient and strictly dependent on low endosomal pH. J Virol. 2007;81:4625–32.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Khan AG, Pickl-Herk A, Gajdzik L, et al. Human rhinovirus 14 enters rhabdomyosarcoma cells expressing icam-1 by a clathrin-, caveolin-, and flotillin-independent pathway. J Virol. 2010;84:3984–92.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Greve JM, Davis G, Meyer AM, et al. The major human rhinovirus receptor is ICAM-1. Cell. 1989;56:839–47.PubMedCrossRefGoogle Scholar
  58. 58.
    Staunton DE, Merluzzi VJ, Rothlein R, et al. A cell adhesion molecule, ICAM-1, is the major surface receptor for rhinoviruses. Cell. 1989;56:849–53.PubMedCrossRefGoogle Scholar
  59. 59.
    Tomassini JE, Graham D, DeWitt CM, et al. cDNA cloning reveals that the major group rhinovirus receptor on HeLa cells is intercellular adhesion molecule 1. Proc Natl Acad Sci U S A. 1989;86:4907–11.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Hofer F, Gruenberger M, Kowalski H, et al. Members of the low density lipoprotein receptor family mediate cell entry of a minor-group common cold virus. Proc Natl Acad Sci U S A. 1994;91:1839–42.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Hubbard AK, Rothlein R. Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling cascades. Free Radic Biol Med. 2000;28:1379–86.PubMedCrossRefGoogle Scholar
  62. 62.
    Staunton DE, Marlin SD, Stratowa C, et al. Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell. 1988;52:925–33.PubMedCrossRefGoogle Scholar
  63. 63.
    Diamond MS, Staunton DE, de Fougerolles AR, et al. ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). J Cell Biol. 1990;111:3129–39.PubMedCrossRefGoogle Scholar
  64. 64.
    Li Y, Cam J, Bu G. Low-density lipoprotein receptor family: endocytosis and signal transduction. Mol Neurobiol. 2001;23:53–67.PubMedCrossRefGoogle Scholar
  65. 65.
    Jeon H, Blacklow SC. Structure and physiologic function of the low-density lipoprotein receptor. Annu Rev Biochem. 2005;74:535–62.PubMedCrossRefGoogle Scholar
  66. 66.
    Beglova N, Blacklow SC. The LDL receptor: how acid pulls the trigger. Trends Biochem Sci. 2005;30:309–17.PubMedCrossRefGoogle Scholar
  67. 67.
    Vignola AM, Chanez P, Campbell AM, et al. Quantification and localization of HLA-DR and intercellular adhesion molecule-1 (ICAM-1) molecules on bronchial epithelial cells of asthmatics using confocal microscopy. Clin Exp Immunol. 1994;96:104–9.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Winther B, Arruda E, Witek TJ, et al. Expression of ICAM-1 in nasal epithelium and levels of soluble ICAM-1 in nasal lavage fluid during human experimental rhinovirus infection. Arch Otolaryngol Head Neck Surg. 2002;128:131–6.PubMedCrossRefGoogle Scholar
  69. 69.
    Kang RS, Folsch H. ARH cooperates with AP-1B in the exocytosis of LDLR in polarized epithelial cells. J Cell Biol. 2011;193:51–60.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Pietiainen V, Vassilev B, Blom T, et al. NDRG1 functions in LDL receptor trafficking by regulating endosomal recycling and degradation. J Cell Sci. 2013;126:3961–71.PubMedCrossRefGoogle Scholar
  71. 71.
    Suomalainen M, Greber UF. Uncoating of non-enveloped viruses. Curr Opin Virol. 2013;3:27–33.PubMedCrossRefGoogle Scholar
  72. 72.
    Greve JM, Forte CP, Marlor CW, et al. Mechanisms of receptor-mediated rhinovirus neutralization defined by two soluble forms of ICAM-1. J Virol. 1991;65:6015–23.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Hoover-Litty H, Greve JM. Formation of rhinovirus-soluble ICAM-1 complexes and conformational changes in the virion. J Virol. 1993;67:390–7.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Nurani G, Lindqvist B, Casasnovas JM. Receptor priming of major group human rhinoviruses for uncoating and entry at mild low-pH environments. J Virol. 2003;77:11985–91.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Schober D, Kronenberger P, Prchla E, et al. Major and minor receptor group human rhinoviruses penetrate from endosomes by different mechanisms. J Virol. 1998;72:1354–64.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Brabec M, Baravalle G, Blaas D, Fuchs R. Conformational changes, plasma membrane penetration, and infection by human rhinovirus type 2: role of receptors and low pH. J Virol. 2003;77:5370–7.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Kolatkar PR, Bella J, Olson NH, et al. Structural studies of two rhinovirus serotypes complexed with fragments of their cellular receptor. EMBO J. 1999;18:6249–59.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Hewat EA, Neumann E, Conway JF, et al. The cellular receptor to human rhinovirus 2 binds around the 5-fold axis and not in the canyon: a structural view. EMBO J. 2000;19:6317–25.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Staunton DE, Gaur A, Chan PY, Springer TA. Internalization of a major group human rhinovirus does not require cytoplasmic or transmembrane domains of ICAM-1. J Immunol. 1992;148:3271–4.PubMedGoogle Scholar
  80. 80.
    Lau C, Wang X, Song L, et al. Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization. J Immunol. 2008;180:870–80.PubMedCrossRefGoogle Scholar
  81. 81.
    Sanderson MP, Lau CW, Schnapp A, Chow CW. Syk: a novel target for treatment of inflammation in lung disease. Inflamm Allergy Drug Targets. 2009;8:87–95.PubMedCrossRefGoogle Scholar
  82. 82.
    Grassme H, Riehle A, Wilker B, Gulbins E. Rhinoviruses infect human epithelial cells via ceramide-enriched membrane platforms. J Biol Chem. 2005;280:26256–62.PubMedCrossRefGoogle Scholar
  83. 83.
    Dreschers S, Franz P, Dumitru C, et al. Infections with human rhinovirus induce the formation of distinct functional membrane domains. Cell Physiol Biochem. 2007;20:241–54.PubMedGoogle Scholar
  84. 84.
    Halbleib JM, Nelson WJ. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev. 2006;20:3199–214.PubMedCrossRefGoogle Scholar
  85. 85.
    Nelson WJ, Dickinson DJ, Weis WI. Roles of cadherins and catenins in cell-cell adhesion and epithelial cell polarity. Prog Mol Biol Transl Sci. 2013;116:3–23.PubMedCrossRefGoogle Scholar
  86. 86.
    Sotomayor M, Gaudet R, Corey DP. Sorting out a promiscuous superfamily: towards cadherin connectomics. Trends Cell Biol. 2014;24:524–36.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.••
    Bonnelykke K, Sleiman P, Nielsen K, et al. A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations. Nat Genet. 2014;46:51–5. Identifies a novel asthma susceptibility gene CDHR3 that is highly expressed in airway epithelium, and suggests that Y529 variant of CDHR3 is associated with a high risk of severe childhood asthma.PubMedCrossRefGoogle Scholar
  88. 88.
    Ross AJ, Dailey LA, Brighton LE, Devlin RB. Transcriptional profiling of mucociliary differentiation in human airway epithelial cells. Am J Respir Cell Mol Biol. 2007;37:169–85.PubMedCrossRefGoogle Scholar
  89. 89.
    Yanai I, Benjamin H, Shmoish M, et al. Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification. Bioinformatics. 2005;21:650–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Bai J, Smock SL, Jackson Jr GR, et al. Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus. PLoS One. 2015;10:e0118286.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Sajjan U, Wang Q, Zhao Y, et al. Rhinovirus disrupts the barrier function of polarized airway epithelial cells. Am J Respir Crit Care Med. 2008;178:1271–81.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Yeo NK, Jang YJ. Rhinovirus infection-induced alteration of tight junction and adherens junction components in human nasal epithelial cells. Laryngoscope. 2010;120:346–52.PubMedGoogle Scholar
  93. 93.
    Perez-Moreno M, Jamora C, Fuchs E. Sticky business: orchestrating cellular signals at adherens junctions. Cell. 2003;112:535–48.PubMedCrossRefGoogle Scholar
  94. 94.
    Bryant DM, Stow JL. The ins and outs of E-cadherin trafficking. Trends Cell Biol. 2004;14:427–34.PubMedCrossRefGoogle Scholar
  95. 95.
    Daniel JM, Reynolds AB. Tyrosine phosphorylation and cadherin/catenin function. Bioessays. 1997;19:883–91.PubMedCrossRefGoogle Scholar
  96. 96.
    Bhella D. The role of cellular adhesion molecules in virus attachment and entry. Philos Trans R Soc Lond B Biol Sci. 2015;370:20140035.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Coyne CB, Bergelson JM. Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions. Cell. 2006;124:119–31.PubMedCrossRefGoogle Scholar
  98. 98.
    Mengaud J, Ohayon H, Gounon P, et al. E-cadherin is the receptor for internalin, a surface protein required for entry of L. monocytogenes into epithelial cells. Cell. 1996;84:923–32.PubMedCrossRefGoogle Scholar
  99. 99.
    Phan QT, Fratti RA, Prasadarao NV, et al. N-cadherin mediates endocytosis of Candida albicans by endothelial cells. J Biol Chem. 2005;280:10455–61.PubMedCrossRefGoogle Scholar
  100. 100.
    Evangelista K, Franco R, Schwab A, Coburn J. Leptospira interrogans binds to cadherins. PLoS Negl Trop Dis. 2014;8:e2672.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Wang H, Li ZY, Liu Y, et al. Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14. Nat Med. 2011;17:96–104.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Lambrecht BN, Hammad H. Allergens and the airway epithelium response: gateway to allergic sensitization. J Allergy Clin Immunol. 2014;134:499–507.PubMedCrossRefGoogle Scholar
  103. 103.
    Lambrecht BN, Hammad H. Asthma: the importance of dysregulated barrier immunity. Eur J Immunol. 2013;43:3125–37.PubMedCrossRefGoogle Scholar
  104. 104.
    Proud D, Turner RB, Winther B, et al. Gene expression profiles during in vivo human rhinovirus infection: insights into the host response. Am J Respir Crit Care Med. 2008;178:962–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Leigh R, Oyelusi W, Wiehler S, et al. Human rhinovirus infection enhances airway epithelial cell production of growth factors involved in airway remodeling. J Allergy Clin Immunol. 2008;121:1238–45.PubMedCrossRefGoogle Scholar
  106. 106.
    Bochkov YA, Hanson KM, Keles S, et al. Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma. Mucosal Immunol. 2010;3:69–80.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Jakiela B, Gielicz A, Plutecka H, et al. Th2-type cytokine-induced mucus metaplasia decreases susceptibility of human bronchial epithelium to rhinovirus infection. Am J Respir Cell Mol Biol. 2014;51:229–41.PubMedGoogle Scholar
  108. 108.•
    Nakagome K, Bochkov YA, Ashraf S, et al. Effects of rhinovirus species on viral replication and cytokine production. J Allergy Clin Immunol 2014. Provides data showing that RV-B, which are typically associated with less severe illnesses in children, also have lower replication, cellular cytotoxicity and cytokine production in vitro compared with RV-A or RV-C. Google Scholar
  109. 109.
    Mosser AG, Brockman-Schneider R, Amineva S, et al. Similar frequency of rhinovirus-infectible cells in upper and lower airway epithelium. J Infect Dis. 2002;185:734–43.PubMedCrossRefGoogle Scholar
  110. 110.
    Winther B, Greve JM, Gwaltney Jr JM, et al. Surface expression of intercellular adhesion molecule 1 on epithelial cells in the human adenoid. J Infect Dis. 1997;176:523–5.PubMedCrossRefGoogle Scholar
  111. 111.
    Jakiela B, Brockman-Schneider R, Amineva S, et al. Basal cells of differentiated bronchial epithelium are more susceptible to rhinovirus infection. Am J Respir Cell Mol Biol. 2008;38:517–23.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Papi A, Johnston SL. Rhinovirus infection induces expression of its own receptor intercellular adhesion molecule 1 (ICAM-1) via increased NF-kappaB-mediated transcription. J Biol Chem. 1999;274:9707–20.PubMedCrossRefGoogle Scholar
  113. 113.
    Grunberg K, Sharon RF, Hiltermann TJ, et al. Experimental rhinovirus 16 infection increases intercellular adhesion molecule-1 expression in bronchial epithelium of asthmatics regardless of inhaled steroid treatment. Clin Exp Allergy. 2000;30:1015–23.PubMedCrossRefGoogle Scholar
  114. 114.
    Suzuki T, Yamaya M, Kamanaka M, et al. Type 2 rhinovirus infection of cultured human tracheal epithelial cells: role of LDL receptor. Am J Physiol Lung Cell Mol Physiol. 2001;280:L409–20.PubMedGoogle Scholar
  115. 115.•
    Alves MP, Schogler A, Ebener S, et al. Comparison of innate immune responses towards rhinovirus infection of primary nasal and bronch. Respirology. 2016;21:304–12. A recent study showing that both major and minor group RVs induce overall similar responses in nasal and bronchial epithelial cells.ial epithelial cells.PubMedCrossRefGoogle Scholar
  116. 116.
    Schuler BA, Schreiber MT, Li L, et al. Major and minor group rhinoviruses elicit differential signaling and cytokine responses as a function of receptor-mediated signal transduction. PLoS One. 2014;9:e93897.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Grayson MH, Cheung D, Rohlfing MM, et al. Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia. J Exp Med. 2007;204:2759–69.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Cheung DS, Ehlenbach SJ, Kitchens T, et al. Development of atopy by severe paramyxoviral infection in a mouse model. Ann Allergy Asthma Immunol. 2010;105:437–43.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Durrani SR, Montville DJ, Pratt AS, et al. Innate immune responses to rhinovirus are reduced by the high-affinity IgE receptor in allergic asthmatic children. J Allergy Clin Immunol. 2012;130:489–95.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Lachowicz-Scroggins ME, Boushey HA, Finkbeiner WE, Widdicombe JH. Interleukin-13-induced mucous metaplasia increases susceptibility of human airway epithelium to rhinovirus infection. Am J Respir Cell Mol Biol. 2010;43:652–61.PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Korpi-Steiner NL, Bates ME, Lee WM, et al. Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation. J Leukoc Biol. 2006;80:1364–74.PubMedCrossRefGoogle Scholar
  122. 122.
    Harris KG, Coyne CB. Enter at your own risk: how enteroviruses navigate the dangerous world of pattern recognition receptor signaling. Cytokine. 2013;63:230–6.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.•
    Girkin J, Hatchwell L, Foster P, et al. CCL7 and IRF-7 mediate hallmark inflammatory and IFN responses following rhinovirus 1B infection. J Immunol. 2015;194:4924–30. Data reveal an important role of CCL7 and IRF-7 in regulating RV-induced inflammation and interferon responses in a mouse model. PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Brabec-Zaruba M, Pfanzagl B, Blaas D, Fuchs R. Site of human rhinovirus RNA uncoating revealed by fluorescent in situ hybridization. J Virol. 2009;83:3770–7.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Hewson CA, Jardine A, Edwards MR, et al. Toll-like receptor 3 is induced by and mediates antiviral activity against rhinovirus infection of human bronchial epithelial cells. J Virol. 2005;79:12273–9.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Wang Q, Nagarkar DR, Bowman ER, et al. Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses. J Immunol. 2009;183:6989–97.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Parsons KS, Hsu AC, Wark PA. TLR3 and MDA5 signalling, although not expression, is impaired in asthmatic epithelial cells in response to rhinovirus infection. Clin Exp Allergy. 2014;44:91–101.PubMedCrossRefGoogle Scholar
  128. 128.
    Triantafilou K, Vakakis E, Richer EA, et al. Human rhinovirus recognition in non-immune cells is mediated by Toll-like receptors and MDA-5, which trigger a synergetic pro-inflammatory immune response. Virulence. 2011;2:22–9.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.•
    Bosco A, Wiehler S, Proud D. Interferon regulatory factor 7 regulates airway epithelial cell responses to human rhinovirus infection. BMC Genomics. 2016;17:76. Study showing that IRF-7 regulates the expression of RV induced genes involved in antiviral immunity, inflammation, and the response to oxidative stress in cultured human bronchial epithelial cells. PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Slater L, Bartlett NW, Haas JJ, et al. Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium. PLoS Pathog. 2010;6:e1001178.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Calven J, Yudina Y, Uller L. Rhinovirus and dsRNA induce RIG-I-like receptors and expression of interferon beta and lambda1 in human bronchial smooth muscle cells. PLoS One. 2013;8, e62718.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Saba TG, Chung Y, Hong JY, et al. Rhinovirus-induced macrophage cytokine expression does not require endocytosis or replication. Am J Respir Cell Mol Biol. 2014;50:974–84.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Wang Q, Miller DJ, Bowman ER, et al. MDA5 and TLR3 initiate pro-inflammatory signaling pathways leading to rhinovirus-induced airways inflammation and hyperresponsiveness. PLoS Pathog. 2011;7:e1002070.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.••
    Hatchwell L, Collison A, Girkin J, et al. Toll-like receptor 7 governs interferon and inflammatory responses to rhinovirus and is suppressed by IL-5-induced lung eosinophilia. Thorax. 2015;70:854–61. These data from a mouse model study determines that a lack of TLR7 signaling under conditions that mimic a virus-induced asthma exacerbation or its inhibition by IL-5-induced lung eosinophilia impairs IFN production and exaggerates Th2-driven inflammatory responses. PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Unger BL, Ganesan S, Comstock AT, et al. Nod-like receptor X-1 is required for rhinovirus-induced barrier dysfunction in airway epithelial cells. J Virol. 2014;88:3705–18.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of PediatricsSchool of Medicine and Public Health, University of Wisconsin-MadisonMadisonUSA
  2. 2.Department of MedicineSchool of Medicine and Public Health, University of Wisconsin-MadisonMadisonUSA

Personalised recommendations