The Journal of Allergy and Clinical Immunology
Volume 122, Issue 4 , Pages 671-682 , October 2008

Host immune responses to rhinovirus: Mechanisms in asthma

  • John T. Kelly, MD
  • ,
  • William W. Busse, MD

      Affiliations

    • Corresponding Author InformationReprint requests: William W. Busse, MD, University of Wisconsin School of Medicine and Public Health, Department of Allergy and Clinical Immunology, J5/219 CSC, Box 2454, 600 Highland Ave, Madison, WI 53792.

Received 10 July 2008 ,Revised 15 August 2008 ,Accepted 18 August 2008.

References 

  1. Lemanske RF, Jackson DJ, Gangnon RE, Evans MD, Li Z, Shult PA, et al. Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol. 2005;116:571–577
  2. Lee KK, Hegele RG, Manfreda J, Wooldrage K, Becker AB, Ferguson AC, et al. Relationship of early childhood viral exposures to respiratory symptoms, onset of possible asthma and atopy in high risk children: the Canadian Asthma Primary Prevention Study. Pediatr Pulmonol. 2007;42:290–297
  3. Johnston SL, Pattemore PK, Sanderson G, Smith S, Campbell MJ, Josephs LK, et al. The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis. Am J Respir Crit Care Med. 1996;154:654–660
  4. Nicholson KG, Kent J, Ireland DC. Respiratory viruses and exacerbations of asthma in adults. BMJ. 1993;307:982–986
  5. Khetsuriani N, Kazerouni NN, Erdman DD, Lu XY, Redd SC, Anderson LJ, et al. Prevalence of viral respiratory tract infections in children with asthma. J Allergy Clin Immunol. 2007;119:314–321
  6. Wos M, Sanak M, Soja J, Olechnowicz H, Busse WW, Szczeklik A. The presence of rhinovirus in lower airways of patients with bronchial asthma. Am J Respir Crit Care Med. 2008;177:1082–1089
  7. Tapparel C, Junier T, Gerlach D, Cordey S, Van Belle S, Perrin L, et al. New complete genome sequences of human rhinoviruses shed light on their phylogeny and genomic features. BMC Genomics. 2007;8:224
  8. Ledford RM, Patel NR, Demenczuk TM, Watanyar A, Herbertz T, Collett MS, et al. VP1 sequencing of all human rhinovirus serotypes: insights into genus phylogeny and susceptibility to antiviral capsid-binding compounds. J Virol. 2004;78:3663–3674
  9. Greenberg SB. Respiratory consequences of rhinovirus infection. Arch Intern Med. 2003;163:278–284
  10. Oberste MS, Maher K, Kilpatrick DR, Pallansch MA. Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. J Virol. 1999;73:1941–1948
  11. Andries K, Dewindt B, Snoeks J, Wouters L, Moereels H, Lewi PJ, et al. Two groups of rhinoviruses revealed by a panel of antiviral compounds present sequence divergence and differential pathogenicity. J Virol. 1990;64:1117–1123
  12. Lau SK, Yip CC, Tsoi HW, Lee RA, So LY, Lau YL, 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;45:3655–3664
  13. Lee WM, Kiesner C, Pappas T, Lee I, Grindle K, Jartti T, et al. A diverse group of previously unrecognized human rhinoviruses are common causes of respiratory illnesses in infants. PLoS ONE. 2007;2:1–11
  14. Heymann PW, Carper HT, Murphy DD, Platts-Mills TA, Patrie J, McLaughlin AP, et al. Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing. J Allergy Clin Immunol. 2004;114:239–247
  15. Gern JE, Busse WW. Relationship of viral infections to wheezing illnesses and asthma. Nat Rev Immunol. 2002;2:132–138
  16. McFadden ER, Pichurko BM, Bowman HF, Ingenito E, Burns S, Dowling N, et al. Thermal mapping of the airways in humans. J Appl Physiol. 1985;58:564–570
  17. Papadopoulos NG, Sanderson G, Hunter J, Johnston SL. Rhinoviruses replicate effectively at lower airway temperatures. J Med Virol. 1999;58:100–104
  18. Schroth MK, Grimm E, Frindt P, Galagan DM, Konno SI, Love R, et al. Rhinovirus replication causes RANTES production in primary bronchial epithelial cells. Am J Respir Cell Mol Biol. 1999;20:1220–1228
  19. Gern JE, Galagan DM, Jarjour NN, Dick EC, Busse WW. Detection of rhinovirus RNA in lower airway cells during experimentally induced infection. Am J Respir Crit Care Med. 1997;155:1159–1161
  20. Malmstrom K, Pitkaranta A, Carpen O, Pelkonen A, Malmberg LP, Turpeinen M, et al. Human rhinovirus in bronchial epithelium of infants with recurrent respiratory symptoms. J Allergy Clin Immunol. 2006;118:591–596
  21. Greve JM, Davis G, Meyer AM, Forte CP, Yost SC, Marlor CW, et al. The major human rhinovirus receptor is ICAM-1. Cell. 1989;56:839–847
  22. Hofer F, Gruenberger M, Kowalski H, Machat H, Huettinger M, Kuechler E, 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;91:1839–1842
  23. Smith CW, Marlin SD, Rothlein R, Toman C, Anderson DC. Cooperative interactions of LFA-1 and Mac-1 with intercellular adhesion molecule-1 in facilitating adherence and transendothelial migration of human neutrophils in vitro. J Clin Invest. 1989;83:2008–2017
  24. 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;274:9707–9720
  25. Chen Y, Hamati E, Lee PK, Lee WM, Wachi S, Schnurr D, et al. Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways. Am J Respir Cell Mol Biol. 2006;34:192–203
  26. Papadopoulos NG, Papi A, Meyer J, Stanciu LA, Salvi S, Holgate ST, et al. Rhinovirus infection up-regulates eotaxin and eotaxin-2 expression in bronchial epithelial cells. Clin Exp Allergy. 2001;31:1060–1066
  27. Zhu Z, Tang W, Gwaltney JM, Wu Y, Elias JA. Rhinovirus stimulation of interleukin-8 in vivo and in vitro: role of NF-kappaB. Am J Physiol. 1997;273:L814–L824
  28. Terajima M, Yamaya M, Sekizawa K, Okinaga S, Suzuki T, Yamada N, et al. Rhinovirus infection of primary cultures of human tracheal epithelium: role of ICAM-1 and IL-1beta. Am J Physiol. 1997;273:L749–L759
  29. Gern JE, Dick EC, Lee WM, Murray S, Meyer K, Handzel ZT, et al. Rhinovirus enters but does not replicate inside monocytes and airway macrophages. J Immunol. 1996;156:621–627
  30. Laza-Stanca V, Stanciu LA, Message SD, Edwards MR, Gern JE, Johnston SL. Rhinovirus replication in human macrophages induces NF-kappaB-dependent tumor necrosis factor alpha production. J Virol. 2006;80:8248–8258
  31. Johnston SL, Papi A, Monick MM, Hunninghake GW. Rhinoviruses induce interleukin-8 mRNA and protein production in human monocytes. J Infect Dis. 1997;175:323–329
  32. Parry DE, Busse WW, Sukow KA, Dick CR, Swenson C, Gern JE. Rhinovirus-induced PBMC responses and outcome of experimental infection in allergic subjects. J Allergy Clin Immunol. 2000;105:692–698
  33. Wolpe SD, Cerami A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. FASEB J. 1989;3:2565–2573
  34. Bloemen PG, van den Tweel MC, Henricks PA, Engels F, Wagenaar SS, Rutten AA, et al. Expression and modulation of adhesion molecules on human bronchial epithelial cells. Am J Respir Cell Mol Biol. 1993;9:586–593
  35. Subauste MC, Jacoby DB, Richards SM, Proud D. Infection of a human respiratory epithelial cell line with rhinovirus: induction of cytokine release and modulation of susceptibility to infection by cytokine exposure. J Clin Invest. 1995;96:549–557
  36. Fahy JV, Kim KW, Liu J, Boushey HA. Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol. 1995;95:843–852
  37. Gern JE, Vrtis R, Grindle KA, Swenson C, Busse WW. Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection. Am J Respir Crit Care Med. 2000;162:2226–2231
  38. Jarjour NN, Gern JE, Kelly EA, Swenson CA, Dick CR, Busse WW. The effect of an experimental rhinovirus 16 infection on bronchial lavage neutrophils. J Allergy Clin Immunol. 2000;105:1169–1177
  39. Wark PA, Johnston SL, Moric I, Simpson JL, Hensley MJ, Gibson PG. Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma. Eur Respir J. 2002;19:68–75
  40. Schuster A, Fahy JV, Ueki I, Nadel JA. Cystic fibrosis sputum induces a secretory response from airway gland serous cells that can be prevented by neutrophil protease inhibitors. Eur Respir J. 1995;8:10–14
  41. Fraenkel DJ, Bardin PG, Sanderson G, Lampe F, Johnston SL, Holgate ST. Lower airways inflammation during rhinovirus colds in normal and in asthmatic subjects. Am J Respir Crit Care Med. 1995;151:879–886
  42. Grunberg K, Smits HH, Timmers MC, de Klerk EP, Dolhain RJ, Dick EC, et al. Experimental rhinovirus 16 infection: effects on cell differentials and soluble markers in sputum in asthmatic subjects. Am J Respir Crit Care Med. 1997;156:609–616
  43. Pacifico L, Iacobini M, Viola F, Werner B, Mancuso G, Chiesa C. Chemokine concentrations in nasal washings of infants with rhinovirus illnesses. Clin Infect Dis. 2000;31:834–838
  44. Rosenberg HF, Domachowske JB. Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens. J Leukoc Biol. 2001;70:691–698
  45. Phipps S, Lam CE, Mahalingam S, Newhouse M, Ramirez R, Rosenberg HF, et al. Eosinophils contribute to innate antiviral immunity and promote clearance of respiratory syncytial virus. Blood. 2007;110:1578–1586
  46. Avila PC, Abisheganaden JA, Wong H, Liu J, Yagi S, Schnurr D, et al. Effects of allergic inflammation of the nasal mucosa on the severity of rhinovirus 16 cold. J Allergy Clin Immunol. 2000;105:923–932
  47. Jatakanon A, Lim S, Barnes PJ. Changes in sputum eosinophils predict loss of asthma control. Am J Respir Crit Care Med. 2000;161:64–72
  48. Wang HB, Ghiran I, Matthaei K, Weller PF. Airway eosinophils: allergic inflammation recruited professional antigen-presenting cells. J Immunol. 2007;179:7585–7592
  49. Padigel UM, Lee JJ, Nolan TJ, Schad GA, Abraham D. Eosinophils can function as antigen-presenting cells to induce primary and secondary immune responses to Strongyloides stercoralis. Infect Immun. 2006;74:3232–3238
  50. Lucey DR, Nicholson-Weller A, Weller PF. Mature human eosinophils have the capacity to express HLA-DR. Proc Natl Acad Sci U S A. 1989;86:1348–1351
  51. Weller PF, Rand TH, Barrett T, Elovic A, Wong DT, Finberg RW. Accessory cell function of human eosinophils: HLA-DR-dependent, MHC-restricted antigen-presentation and IL-1 alpha expression. J Immunol. 1993;150:2554–2562
  52. Guida L, O'Hehir RE, Hawrylowicz CM. Synergy between dexamethasone and interleukin-5 for the induction of major histocompatibility complex class II expression by human peripheral blood eosinophils. Blood. 1994;84:2733–2740
  53. Hansel TT, Braunstein JB, Walker C, Blaser K, Bruijnzeel PL, Virchow JC, et al. Sputum eosinophils from asthmatics express ICAM-1 and HLA-DR. Clin Exp Immunol. 1991;86:271–277
  54. Sedgwick JB, Calhoun WJ, Vrtis RF, Bates ME, McAllister PK, Busse WW. Comparison of airway and blood eosinophil function after in vivo antigen challenge. J Immunol. 1992;149:3710–3718
  55. Ohkawara Y, Lim KG, Xing Z, Glibetic M, Nakano K, Dolovich J, et al. CD40 expression by human peripheral blood eosinophils. J Clin Invest. 1996;97:1761–1766
  56. Handzel ZT, Busse WW, Sedgwick JB, Vrtis R, Lee WM, Kelly EA, et al. Eosinophils bind rhinovirus and activate virus-specific T cells. J Immunol. 1998;160:1279–1284
  57. Mawhorter SD, Kazura JW, Boom WH. Human eosinophils as antigen-presenting cells: relative efficiency for superantigen- and antigen-induced CD4+ T-cell proliferation. Immunology. 1994;81:584–591
  58. Levandowski RA, Ou DW, Jackson GG. Acute-phase decrease of T lymphocyte subsets in rhinovirus infection. J Infect Dis. 1986;153:743–748
  59. Wark PA, Bucchieri F, Johnston SL, Gibson PG, Hamilton L, Mimica J, et al. IFN-gamma-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations. J Allergy Clin Immunol. 2007;120:586–593
  60. Rabin RL, Park MK, Liao F, Swofford R, Stephany D, Farber JM. Chemokine receptor responses on T cells are achieved through regulation of both receptor expression and signaling. J Immunol. 1999;162:3840–3850
  61. Spurrell JC, Wiehler S, Zaheer RS, Sanders SP, Proud D. Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection. Am J Physiol Lung Cell Mol Physiol. 2005;289:L85–L95
  62. Odemuyiwa SO, Ghahary A, Li Y, Puttagunta L, Lee JE, Musat-Marcu S, et al. Cutting edge: human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase. J Immunol. 2004;173:5909–5913
  63. Message SD, Johnston SL. The immunology of virus infection in asthma. Eur Respir J. 2001;18:1013–1025
  64. Alper CM, Doyle WJ, Skoner DP, Buchman CA, Seroky JT, Gwaltney JM, et al. Prechallenge antibodies: moderators of infection rate, signs, and symptoms in adults experimentally challenged with rhinovirus type 39. Laryngoscope. 1996;106:1298–1305
  65. Welliver RC, Wong DT, Sun M, Middleton EJ, Vaughan RS, Ogra PL. The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med. 1981;305:841–846
  66. Skoner DP, Doyle WJ, Tanner EP, Kiss J, Fireman P. Effect of rhinovirus 39 (RV-39) infection on immune and inflammatory parameters in allergic and non-allergic subjects. Clin Exp Allergy. 1995;25:561–567
  67. Gern JE, Martin MS, Anklam KA, Shen K, Roberg KA, Carlson-Dakes KT, et al. Relationships among specific viral pathogens, virus-induced interleukin-8, and respiratory symptoms in infancy. Pediatr Allergy Immunol. 2002;13:386–393
  68. van Benten IJ, KleinJan A, Neijens HJ, Osterhaus AD, Fokkens WJ. Prolonged nasal eosinophilia in allergic patients after common cold. Allergy. 2001;56:949–956
  69. Grissell TV, Powell H, Shafren DR, Boyle MJ, Hensley MJ, Jones PD, et al. Interleukin-10 gene expression in acute virus-induced asthma. Am J Respir Crit Care Med. 2005;172:433–439
  70. Schall TJ, Bacon K, Camp RD, Kaspari JW, Goeddel DV. Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes. J Exp Med. 1993;177:1821–1826
  71. Gentile DA, Fireman P, Skoner DP. Elevations of local leukotriene C4 levels during viral upper respiratory tract infections. Ann Allergy Asthma Immunol. 2003;91:270–274
  72. Jame AJ, Lackie PM, Cazaly AM, Sayers I, Penrose JF, Holgate ST, et al. Human bronchial epithelial cells express an active and inducible biosynthetic pathway for leukotrienes B4 and C4. Clin Exp Allergy. 2007;37:880–892
  73. Wark PA, Johnston SL, Bucchieri F, Powell R, Puddicombe S, Laza-Stanca V, et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med. 2005;201:937–947
  74. Contoli M, Message SD, Laza-Stanca V, Edwards MR, Wark PA, Bartlett NW, et al. Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med. 2006;12:1023–1026
  75. Kling S, Donninger H, Williams Z, Vermeulen J, Weinberg E, Latiff K, et al. Persistence of rhinovirus RNA after asthma exacerbation in children. Clin Exp Allergy. 2005;35:672–678
  76. Corne JM, Marshall C, Smith S, Schreiber J, Sanderson G, Holgate ST, et al. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet. 2002;359:831–834
  77. Papadopoulos NG, Stanciu LA, Papi A, Holgate ST, Johnston SL. A defective type 1 response to rhinovirus in atopic asthma. Thorax. 2002;57:328–332
  78. Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63(suppl 86):8-160
  79. Duff AL, Pomeranz ES, Gelber LE, Price GW, Farris H, Hayden FG, et al. Risk factors for acute wheezing in infants and children: viruses, passive smoke and IgE antibodies to inhalant allergens. Pediatrics. 1993;92:535–540
  80. Heymann PW, Rakes GP, Hogan AD, Ingram JM, Hoober GE, Plansmills TAE. Assessment of eosinophils, viruses and IgE antibody in wheezing infants and children. Int Arch Allergy Immunol. 1995;107:380–382
  81. Zambrano JC, Carper HT, Rakes GP, Patrie J, Murphy DD, Platts-Mills TAE, et al. Experimental rhinovirus challenges in adults with mild asthma: response to infection in relation to IgE. J Allergy Clin Immunol. 2003;111:1008–1016
  82. Bianco A, Sethi SK, Allen JT, Knight RA, Spiteri MA. Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1. Eur Respir J. 1998;12:619–626
  83. Bianco A, Whiteman SC, Sethi SK, Allen JT, Knight RA, Spiteri MA. Expression of intercellular adhesion molecule-1 (ICAM-1) in nasal epithelial cells of atopic subjects: a mechanism for increased rhinovirus infection?. Clin Exp Immunol. 2000;121:339–345
  84. Murray CS, Poletti G, Kebadze T, Morris J, Woodcock A, Johnston SL, et al. Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax. 2006;61:376–382
  85. Bardin PG, Fraenkel DJ, Sanderson G, Dorward M, Lau LCK, Johnston SL, et al. Amplified rhinovirus colds in atopic subjects. Clin Exp Allergy. 1994;24:457–464
  86. Kluijver JC, Evertse CE, Sont JK, Schrumpf JA, Zeijl-van der Ham JG, Dick CR, et al. Are rhinovirus-induced airway responses in asthma aggravated by chronic allergen exposure?. Am J Respir Crit Care Med. 2003;168:1174–1180
  87. Pauwels RA, Lofdahl CG, Postma DS, Tattersfield AE, O'Byrne P, Barnes PJ, et al. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med. 1997;337:1405–1411
  88. Venarske DL, Busse WW, Griffin MR, Gebretsadik T, Shintani AK, Minton PA, et al. The relationship of rhinovirus-associated asthma hospitalizations with inhaled corticosteroids and smoking. J Infect Dis. 2006;193:1536–1543
  89. Grunberg K, Sharon RF, Sont JK, In 't Veen JC, Van Schadewijk WA, De Klerk EP, et al. Rhinovirus-induced airway inflammation in asthma: effect of treatment with inhaled corticosteroids before and during experimental infection. Am J Respir Crit Care Med. 2001;164:1816–1822
  90. Lehtinen P, Ruohola A, Vanto T, Vuorinen T, Ruuskanen O, Jartti T. Prednisolone reduces recurrent wheezing after a first wheezing episode associated with rhinovirus infection or eczema. J Allergy Clin Immunol. 2007;119:570–575
  91. Brunette MG, Lands L, Thibodeau LP. Childhood asthma prevention of attacks with short-term corticosteroid treatment of upper respiratory tract infection. Pediatrics. 1988;81:624–629
  92. Edwards MR, Haas J, Panettieri RA, Johnson M, Johnston SL. Corticosteroids and beta2 agonists differentially regulate rhinovirus-induced interleukin-6 via distinct Cis-acting elements. J Biol Chem. 2007;282:15366–15375
  93. Pelaia G, Vatrella A, Cuda G, Maselli R, Marsico SA. Molecular mechanisms of corticosteroid actions in chronic inflammatory airway diseases. Life Sci. 2003;72:1549–1561
  94. Pelaia G, Cuda G, Vatrella A, Grembiale RD, De Sarro G, Maselli R, et al. Effects of glucocorticoids on activation of c-jun N-terminal, extracellular signal-regulated, and p38 MAP kinases in human pulmonary endothelial cells. Biochem Pharmacol. 2001;62:1719–1724
  95. Auphan N, DiDonato JA, Rosette C, Helmberg A, Karin M. Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science. 1995;270:286–290
  96. Edwards MR, Mukaida N, Johnson M, Johnston SL. IL-1beta induces IL-8 in bronchial cells via NF-kappaB and NF-IL6 transcription factors and can be suppressed by glucocorticoids. Pulm Pharmacol Ther. 2005;18:337–345
  97. Bisgaard H, Zielen S, Garcia-Garcia ML, Johnston SL, Gilles L, Menten J, et al. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma. Am J Respir Crit Care Med. 2005;171:315–322
  98. Robertson CF, Price D, Henry R, Mellis C, Glasgow N, Fitzgerald D, et al. Short-course montelukast for intermittent asthma in children: a randomized controlled trial. Am J Respir Crit Care Med. 2007;175:323–329
  99. Hayden FG, Albrecht JK, Kaiser DL, Gwaltney JM. Prevention of natural colds by contact prophylaxis with intranasal alpha 2-interferon. N Engl J Med. 1986;314:71–75
  100. Farr BM, Gwaltney JM, Adams KF, Hayden FG. Intranasal interferon-alpha 2 for prevention of natural rhinovirus colds. Antimicrob Agents Chemother. 1984;26:31–34
  101. Sperber SJ, Hayden FG. Comparative susceptibility of respiratory viruses to recombinant interferons-alpha 2b and -beta. J Interferon Res. 1989;9:285–293
  102. Sperber SJ, Levine PA, Sorrentino JV, Riker DK, Hayden FG. Ineffectiveness of recombinant interferon-beta serine nasal drops for prophylaxis of natural colds. J Infect Dis. 1989;160:700–705
  103. Pevear DC, Hayden FG, Demenczuk TM, Barone LR, McKinlay M, Collett M. Relationship of pleconaril susceptibility and clinical outcomes in treatment of common colds caused by rhinovirus. Antimicrob Agents Chemother. 2005;49:4492–4499
  104. Hayden FG, Herrington DT, Coats TL, Kim K, Cooper EC, Villano SA, et al. Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials. Clin Infect Dis. 2003;36:1523–1532
  105. Fleischer R, Laessig K. Safety and efficacy evaluation of pleconaril for treatment of the common cold. Clin Infect Dis. 2003;37:1722
  106. Stanley MA. Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential. Clin Exp Dermatol. 2002;27:571–577
  107. Clejan S, Mandrea E, Pandrea IV, Dufour J, Japa S, Veazey RS. Immune responses induced by intranasal imiquimod and implications for therapeutics in rhinovirus infections. J Cell Mol Med. 2005;9:457–461
  108. Stokes JR, Sorkness RL, Kaplan MR, Castleman WL, Tomai MA, Miller RL, et al. Attenuation of virus-induced airway dysfunction in rats treated with imiquimod. Eur Respir J. 1998;11:324–329
  109. Hayden FG, Gwaltney JM, Colonno RJ. Modification of experimental rhinovirus colds by receptor blockade. Antiviral Res. 1988;9:233–247
  110. Charles CH, Luo GX, Kohlstaedt LA, Morantte IG, Gorfain E, Cao L, et al. Prevention of human rhinovirus infection by multivalent fab molecules directed against ICAM-1. Antimicrob Agents Chemother. 2003;47:1503–1508
  111. Turner RB, Wecker MT, Pohl G, Witek TJ, McNally E, St George R, et al. Efficacy of tremacamra, a soluble intercellular adhesion molecule 1, for experimental rhinovirus infection: a randomized clinical trial. JAMA. 1999;281:1797–1804
  112. Fendrick AM. Viral respiratory infections due to rhinoviruses: current knowledge, new developments. Am J Ther. 2003;10:193–202
  113. Rotbart HA. Antiviral therapy for enteroviruses and rhinoviruses. Antivir Chem Chemother. 2000;11:261–271
  114. Maugeri C, Alisi MA, Apicella C, Cellai L, Dragone P, Fioravanzo E, et al. New anti-viral drugs for the treatment of the common cold. Bioorg Med Chem. 2008;16:3091–3107
  115. Zalman LS, Brothers MA, Dragovich PS, Zhou R, Prins TJ, Worland ST, et al. Inhibition of human rhinovirus-induced cytokine production by AG7088, a human rhinovirus 3C protease inhibitor. Antimicrob Agents Chemother. 2000;44:1236–1241
  116. Hayden FG, Turner RB, Gwaltney JM, Chi-Burris K, Gersten M, Hsyu P, et al. Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers. Antimicrob Agents Chemother. 2003;47:3907–3916

 (Supported by an educational grant from Merck & Co., Inc.)

 Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD

 Supported by National Institutes of Health–National Heart, Lung, and Blood Institute grant no. HL069116 and National Institutes of Health–National Institute of Allergy and Infectious Diseases grant no. T32 AI007635.

 Terms in boldface and italics are defined in the glossary on page 672.

PII: S0091-6749(08)01506-6

doi: 10.1016/j.jaci.2008.08.013

The Journal of Allergy and Clinical Immunology
Volume 122, Issue 4 , Pages 671-682 , October 2008