JE Gern, DM Galagan, NN Jarjour, EC Dick and WW Busse
Department of Pediatrics, Universin of Wisconsin School of Medicine, Madison, USA.

Rhinovirus (RV) infections are presumed to be localized to the upper airway, yet can cause severe lower airway symptoms in children and adults with asthma. To test the hypothesis that rhinovirus infection of the upper airway may be associated with the presence of virus in lower airway cells, we used the techniques of reverse transcription- polymerase chain reaction (RT-PCR) and Southern blotting to detect RV RNA in lower airway cells from eight allergic volunteers experimentally infected with RV16. Bronchoscopy with bronchoalveolar lavage (BAL) was done 1 mo before, and 2 and 4 d after an experimental infection with RV16. All subjects developed cold symptoms, and infection was confirmed by culturing RV16 from nasal secretions. Rhinovirus RNA was detected in both nasal lavage and lower airway cells from all eight subjects 2 to 4 d after an experimental inoculation, but not in any of the precold specimens from either the nose or the lower airway. These findings suggest that RV can infect cells of the lower airway, and raise the possibility that such an effect can promote asthma exacerbations in the susceptible host through direct enhancement of local inflammation.

This article has been cited by other articles:

				B. Jakiela, R. Brockman-Schneider, S. Amineva, W.-M. Lee, and J. E. Gern Basal Cells of Differentiated Bronchial Epithelium Are More Susceptible to Rhinovirus Infection Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 517 - 523. [Abstract] [Full Text] [PDF]

				F. W. S. Ko, M. Ip, P. K. S. Chan, M. C. H. Chan, K.-W. To, S. S. S. Ng, S. S. L. Chau, J. W. Tang, and D. S. C. Hui Viral Etiology of Acute Exacerbations of COPD in Hong Kong Chest, September 1, 2007; 132(3): 900 - 908. [Abstract] [Full Text] [PDF]

				M. B. Hershenson and S. L. Johnston Rhinovirus Infections: More Than a Common Cold Am. J. Respir. Crit. Care Med., December 15, 2006; 174(12): 1284 - 1285. [Full Text] [PDF]

				L. Kaiser, J.-D. Aubert, J.-C. Pache, C. Deffernez, T. Rochat, J. Garbino, W. Wunderli, P. Meylan, S. Yerly, L. Perrin, et al. Chronic Rhinoviral Infection in Lung Transplant Recipients Am. J. Respir. Crit. Care Med., December 15, 2006; 174(12): 1392 - 1399. [Abstract] [Full Text] [PDF]

				N. L. Korpi-Steiner, M. E. Bates, W.-M. Lee, D. J. Hall, and P. J. Bertics 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., December 1, 2006; 80(6): 1364 - 1374. [Abstract] [Full Text] [PDF]

				P A B Wark and P G Gibson Asthma exacerbations {middle dot} 3: Pathogenesis. Thorax, October 1, 2006; 61(10): 909 - 915. [Abstract] [Full Text] [PDF]

				U. S. Sajjan, Y. Jia, D. C. Newcomb, J. K. Bentley, N. W. Lukacs, J. J. LiPuma, and M. B. Hershenson H. influenzae potentiates airway epithelial cell responses to rhinovirus by increasing ICAM-1 and TLR3 expression FASEB J, October 1, 2006; 20(12): 2121 - 2123. [Abstract] [Full Text] [PDF]

				S. Carraro, J. Doherty, K. Zaman, I. Gainov, R. Turner, J. Vaughan, J. F. Hunt, J. Marquez, and B. Gaston S-nitrosothiols regulate cell-surface pH buffering by airway epithelial cells during the human immune response to rhinovirus Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L827 - L832. [Abstract] [Full Text] [PDF]

				Y. Chen, E. Hamati, P.-K. Lee, W.-M. Lee, S. Wachi, D. Schnurr, S. Yagi, G. Dolganov, H. Boushey, P. Avila, et al. Rhinovirus Induces Airway Epithelial Gene Expression through Double-Stranded RNA and IFN-Dependent Pathways Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 192 - 203. [Abstract] [Full Text] [PDF]

				Poster presentations Thorax, December 1, 2005; 60(suppl_2): ii53 - ii120. [Full Text] [PDF]

				M. Xatzipsalti, S. Kyrana, M. Tsolia, S. Psarras, A. Bossios, V. Laza-Stanca, S. L. Johnston, and N. G. Papadopoulos Rhinovirus Viremia in Children with Respiratory Infections Am. J. Respir. Crit. Care Med., October 15, 2005; 172(8): 1037 - 1040. [Abstract] [Full Text] [PDF]

				W. W. Busse, A. Wanner, K. Adams, H. Y. Reynolds, M. Castro, B. Chowdhury, M. Kraft, R. J. Levine, S. P. Peters, and E. J. Sullivan Investigative Bronchoprovocation and Bronchoscopy in Airway Diseases Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 807 - 816. [Abstract] [Full Text] [PDF]

				P. A.B. Wark, S. L. Johnston, F. Bucchieri, R. Powell, S. Puddicombe, V. Laza-Stanca, S. T. Holgate, and D. E. Davies Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus J. Exp. Med., March 21, 2005; 201(6): 937 - 947. [Abstract] [Full Text] [PDF]

				A. G. Mosser, R. Vrtis, L. Burchell, W.-M. Lee, C. R. Dick, E. Weisshaar, D. Bock, C. A. Swenson, R. D. Cornwell, K. C. Meyer, et al. Quantitative and Qualitative Analysis of Rhinovirus Infection in Bronchial Tissues Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 645 - 651. [Abstract] [Full Text] [PDF]

				C. S. Murray, A. Simpson, and A. Custovic Allergens, Viruses, and Asthma Exacerbations Proceedings of the ATS, April 1, 2004; 1(2): 99 - 104. [Abstract] [Full Text] [PDF]

				J. A. Wedzicha Role of Viruses in Exacerbations of Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2004; 1(2): 115 - 120. [Abstract] [Full Text] [PDF]

				S. D. Message and S. L. Johnston Host defense function of the airway epithelium in health and disease: clinical background J. Leukoc. Biol., January 1, 2004; 75(1): 5 - 17. [Abstract] [Full Text] [PDF]

				G. D. Brooks, K. A. Buchta, C. A. Swenson, J. E. Gern, and W. W. Busse Rhinovirus-induced Interferon-{gamma} and Airway Responsiveness in Asthma Am. J. Respir. Crit. Care Med., November 1, 2003; 168(9): 1091 - 1094. [Abstract] [Full Text] [PDF]

				R. F. Lemanske Jr. Is Asthma an Infectious Disease?: Thomas A. Neff Lecture Chest, March 1, 2003; 123(2007): 385S - 390S. [Abstract] [Full Text] [PDF]

				J. de Kluijver, K. Grunberg, J.K. Sont, M. Hoogeveen, W.A.A.M. van Schadewijk, E.P.A. de Klerk, C.R. Dick, J.H.J.M. van Krieken, and P.J. Sterk Rhinovirus infection in nonasthmatic subjects: effects on intrapulmonary airways Eur. Respir. J., August 1, 2002; 20(2): 274 - 279. [Abstract] [Full Text] [PDF]

				S. D Message and S. L Johnston Viruses in asthma: The role of viruses in childhood respiratory infections Br. Med. Bull., March 1, 2002; 61(1): 29 - 43. [Abstract] [Full Text] [PDF]

				G. Boivin, A. D. Osterhaus, A. Gaudreau, H. C. Jackson, J. Groen, and P. Ward Role of Picornaviruses in Flu-Like Illnesses of Adults Enrolled in an Oseltamivir Treatment Study Who Had No Evidence of Influenza Virus Infection J. Clin. Microbiol., February 1, 2002; 40(2): 330 - 334. [Abstract] [Full Text] [PDF]

				S.D. Message and S.L. Johnston The immunology of virus infection in asthma Eur. Respir. J., December 1, 2001; 18(6): 1013 - 1025. [Abstract] [Full Text] [PDF]

				K. GRUNBERG, R. F. SHARON, J. K. SONT, J. C. C. M. IN'T VEEN, W. A. A. M. VAN SCHADEWIJK, E. P. A. DE KLERK, C. R. DICK, J. H. J. M. VAN KRIEKEN, and P. J. STERK Rhinovirus-induced Airway Inflammation in Asthma . Effect of Treatment with Inhaled Corticosteroids before and during Experimental Infection Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1816 - 1822. [Abstract] [Full Text] [PDF]

				T. SEEMUNGAL, R. HARPER-OWEN, A. BHOWMIK, I. MORIC, G. SANDERSON, S. MESSAGE, P. MACCALLUM, T. W. MEADE, D. J. JEFFRIES, S. L. JOHNSTON, et al. Respiratory Viruses, Symptoms, and Inflammatory Markers in Acute Exacerbations and Stable Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., November 1, 2001; 164(9): 1618 - 1623. [Abstract] [Full Text] [PDF]

				M.C. Mckean, M. Leech, P.C. Lambert, C. Hewitt, S. Myint, and M. Silverman A model of viral wheeze in nonasthmatic adults: symptoms and physiology Eur. Respir. J., July 1, 2001; 18(1): 23 - 32. [Abstract] [Full Text] [PDF]

				P MAESTRELLI, L RICHELDI, M MORETTI, and L M FABBRI Analysis of sputum in COPD Thorax, June 1, 2001; 56(6): 420 - 422. [Full Text]

				J. E. GERN, R. VRTIS, K. A. GRINDLE, C. SWENSON, and W. W. BUSSE Relationship of Upper and Lower Airway Cytokines to Outcome of Experimental Rhinovirus Infection Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2226 - 2231. [Abstract] [Full Text]

				T. FRISCHER and E. BARALDI Upper Airway Sampling Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): S28 - 30. [Full Text] [PDF]

				J. A. DOUGLASS and R. E. O'HEHIR What Determines Asthma Phenotype? . Respiratory Infections and Asthma Am. J. Respir. Crit. Care Med., March 1, 2000; 161(3): S211 - 214. [Full Text] [PDF]

				A. Papi and S. L. Johnston Respiratory Epithelial Cell Expression of Vascular Cell Adhesion Molecule-1 and Its Up-regulation by Rhinovirus Infection via NF-kappa B and GATA Transcription Factors J. Biol. Chem., October 15, 1999; 274(42): 30041 - 30051. [Abstract] [Full Text] [PDF]

				H. E. FLEMING, F. F. LITTLE, D. SCHNURR, P. C. AVILA, H. WONG, J. LIU, S. YAGI, and H. A. BOUSHEY Rhinovirus-16 Colds in Healthy and in Asthmatic Subjects . Similar Changes in Upper and Lower Airways Am. J. Respir. Crit. Care Med., July 1, 1999; 160(1): 100 - 108. [Abstract] [Full Text]

				M. K. Schroth, E. Grimm, P. Frindt, D. M. Galagan, S.-I. Konno, R. Love, and J. E. Gern Rhinovirus Replication Causes RANTES Production in Primary Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., June 1, 1999; 20(6): 1220 - 1228. [Abstract] [Full Text]

				A. Papi and S. L. Johnston Rhinovirus Infection Induces Expression of Its Own Receptor Intercellular Adhesion Molecule 1 (ICAM-1) via Increased NF-kappa B-mediated Transcription J. Biol. Chem., April 2, 1999; 274(14): 9707 - 9720. [Abstract] [Full Text] [PDF]

				L. KAINULAINEN, J. NIKOSKELAINEN, T. VUORINEN, K. TEVOLA, K. LIIPPO, and O. RUUSKANEN Viruses and Bacteria in Bronchial Samples from Patients with Primary Hypogammaglobulinemia Am. J. Respir. Crit. Care Med., April 1, 1999; 159(4): 1199 - 1204. [Abstract] [Full Text] [PDF]

				A. DAKHAMA, R. G. HEGELE, G. LAFLAMME, E. ISRAeL-ASSAYAG, and Y. CORMIER Common Respiratory Viruses in Lower Airways of Patients with Acute Hypersensitivity Pneumonitis Am. J. Respir. Crit. Care Med., April 1, 1999; 159(4): 1316 - 1322. [Abstract] [Full Text] [PDF]

				G. P. RAKES, E. ARRUDA, J. M. INGRAM, G. E. HOOVER, J. C. ZAMBRANO, F. G. HAYDEN, T. A. E. PLATTS-MILLS, and P. W. HEYMANN Rhinovirus and Respiratory Syncytial Virus in Wheezing Children Requiring Emergency Care . IgE and Eosinophil Analyses Am. J. Respir. Crit. Care Med., March 1, 1999; 159(3): 785 - 790. [Abstract] [Full Text]

				J. E. Gern and W. W. Busse Association of Rhinovirus Infections with Asthma Clin. Microbiol. Rev., January 1, 1999; 12(1): 9 - 18. [Abstract] [Full Text] [PDF]

				N G PAPADOPOULOS and S L JOHNSTON Viruses and asthma exacerbations Thorax, November 1, 1998; 53(11): 913 - 914. [Full Text]

				S. L. Johnston, A. Papi, P. J. Bates, J. G. Mastronarde, M. M. Monick, and G. W. Hunninghake Low Grade Rhinovirus Infection Induces a Prolonged Release of IL-8 in Pulmonary Epithelium J. Immunol., June 15, 1998; 160(12): 6172 - 6181. [Abstract] [Full Text] [PDF]

				G. FOLKERTS, W. W. BUSSE, F. P. NIJKAMP, R. SORKNESS, and J. E. GERN Virus-induced Airway Hyperresponsiveness and Asthma Am. J. Respir. Crit. Care Med., June 1, 1998; 157(6): 1708 - 1720. [Full Text] [PDF]

				K. GRÜNBERG, H. H. SMITS, M. C. TIMMERS, E. P. A. de KLERK, R. J. E. M. DOLHAIN, E. C. DICK, P. S. HIEMSTRA, and P. J. STERK Experimental Rhinovirus 16 Infection . Effects on Cell Differentials and Soluble Markers in Sputum in Asthmatic Subjects Am. J. Respir. Crit. Care Med., July 1, 1997; 156(2): 609 - 616. [Abstract] [Full Text]