PG Bardin, SL Johnston, G Sanderson, BS Robinson, MA Pickett, DJ Fraenkel and ST Holgate
Immunopharmacology Group, Southampton General Hospital, United Kingdom.

Human rhinoviruses (HRVs) cause the common cold and often induce lower airway symptoms such as cough and wheezing. Although HRV infection is presumed to involve primarily ciliated epithelial cells, this has not been confirmed in vivo, and the cellular distribution and spread of infection as well as the pathogenesis of cold related nasal and chest symptoms remain speculative. We have developed in situ hybridization (ISH) to explore localization of the virus to airway tissues, employing HRV 16-derived oligonucleotide probes after sequencing part of the genome of this serotype. A reverse transcription-polymerase chain reaction was used to generate DNA from HRV 16 for sequencing; this yielded 305 nucleotide bases that showed considerable homology to other HRVs. The HRV 16 sequence was used to design oligonucleotides functioning as antisense and sense probes. These probes as well as random sequence and pathogen control oligonucleotides were applied to HRV-infected cell-clot complexes and finally to sections from six paired nasal biopsies obtained before, during, or after HRV-proven colds. Specificity of hybrids was established by the absence of signal in uninfected tissue, in cells infected with other viruses, after RNase pretreatment, and with application of control probes. Hybridization signals were observed in epithelial cells in three of six biopsies obtained during a cold, using probes to viral (+) strand; intermediate (-) strand, implying viral replication, was present in one biopsy. Evidence for infection of nonepithelial cells was inconclusive. HRVs cause productive infection of nasal epithelium during a cold and their intracellular localization may produce perturbation of inflammatory mediators and cytokine profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				S. Wiehler and D. Proud Interleukin-17A modulates human airway epithelial responses to human rhinovirus infection Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L505 - L515. [Abstract] [Full Text] [PDF]

				V. Laza-Stanca, L. A. Stanciu, S. D. Message, M. R. Edwards, J. E. Gern, and S. L. Johnston Rhinovirus Replication in Human Macrophages Induces NF-{kappa}B-Dependent Tumor Necrosis Factor Alpha Production. J. Virol., August 1, 2006; 80(16): 8248 - 8258. [Abstract] [Full Text] [PDF]

				S. Kauder, S. Kan, and V. R. Racaniello Age-Dependent Poliovirus Replication in the Mouse Central Nervous System Is Determined by Internal Ribosome Entry Site-Mediated Translation J. Virol., March 15, 2006; 80(6): 2589 - 2595. [Abstract] [Full Text] [PDF]

				J. C. L. Spurrell, S. Wiehler, R. S. Zaheer, S. P. Sanders, and D. Proud Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L85 - L95. [Abstract] [Full Text] [PDF]

				D. Proud, S. P. Sanders, and S. Wiehler Human Rhinovirus Infection Induces Airway Epithelial Cell Production of Human {beta}-Defensin 2 Both In Vitro and In Vivo J. Immunol., April 1, 2004; 172(7): 4637 - 4645. [Abstract] [Full Text] [PDF]

				N. Lopez-Souza, G. Dolganov, R. Dubin, L. A. Sachs, L. Sassina, H. Sporer, S. Yagi, D. Schnurr, H. A. Boushey, and J. H. Widdicombe Resistance of differentiated human airway epithelium to infection by rhinovirus Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L373 - L381. [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]

				K. Loens, M. Ieven, D. Ursi, C. de Laat, P. Sillekens, P. Oudshoorn, and H. Goossens Improved Detection of Rhinoviruses by Nucleic Acid Sequence-Based Amplification after Nucleotide Sequence Determination of the 5' Noncoding Regions of Additional Rhinovirus Strains J. Clin. Microbiol., May 1, 2003; 41(5): 1971 - 1976. [Abstract] [Full Text] [PDF]

				S. P. Sanders, J. Kim, K. Ryan Connolly, J. D. Porter, E. S. Siekierski, and D. Proud Nitric Oxide Inhibits Rhinovirus-Induced Granulocyte Macrophage Colony-Stimulating Factor Production in Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., March 1, 2001; 24(3): 317 - 325. [Abstract] [Full Text] [PDF]

				J. Kim, S. P. Sanders, E. S. Siekierski, V. Casolaro, and D. Proud Role of NF-{kappa}B in Cytokine Production Induced from Human Airway Epithelial Cells by Rhinovirus Infection J. Immunol., September 15, 2000; 165(6): 3384 - 3392. [Abstract] [Full Text] [PDF]

				H. A. Rotbart and F. G. Hayden Picornavirus Infections: A Primer for the Practitioner Arch Fam Med, September 1, 2000; 9(9): 913 - 920. [Abstract] [Full Text] [PDF]

				L. S. Zalman, M. A. Brothers, P. S. Dragovich, R. Zhou, T. J. Prins, S. T. Worland, and A. K. Patick Inhibition of Human Rhinovirus-Induced Cytokine Production by AG7088, a Human Rhinovirus 3C Protease Inhibitor Antimicrob. Agents Chemother., May 1, 2000; 44(5): 1236 - 1241. [Abstract] [Full Text]

				M. Yamaya, K. Sekizawa, T. Suzuki, N. Yamada, M. Furukawa, S. Ishizuka, K. Nakayama, M. Terajima, Y. Numazaki, and H. Sasaki Infection of human respiratory submucosal glands with rhinovirus: effects on cytokine and ICAM-1 production Am J Physiol Lung Cell Mol Physiol, August 1, 1999; 277(2): L362 - L371. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				S. P. Sanders, E. S. Siekierski, J. D. Porter, S. M. Richards, and D. Proud Nitric Oxide Inhibits Rhinovirus-Induced Cytokine Production and Viral Replication in a Human Respiratory Epithelial Cell Line J. Virol., February 1, 1998; 72(2): 934 - 942. [Abstract] [Full Text] [PDF]