TY - JOUR
T1 - In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects
AU - Lopez-Souza, Nilceia
AU - Favoreto, Silvio
AU - Wong, Hofer
AU - Ward, Theresa
AU - Yagi, Shigeo
AU - Schnurr, David
AU - Finkbeiner, Walter E.
AU - Dolganov, Gregory M.
AU - Widdicombe, Jonathan H.
AU - Boushey, Homer A.
AU - Avila, Pedro C.
N1 - Funding Information:
Disclosure of potential conflict of interest: W. E. Finkbeiner has received research support from the Cystic Fibrosis Foundation and the National Institutes of Health. G. M. Dolganov has provided legal consultation or expert witness testimony on the topic of gene expression assays. J. H. Widdicombe has received research support from Cystic Fibrosis Research, Inc. H. A. Boushey has received research support from GlaxoSmithKline and honoraria from Genentech and Novartis and has served as a member and chair of the Health Effect's Institute's review committee. P. C. Avila has received research support from Genentech. The rest of the authors have declared that they have no conflict of interest.
Funding Information:
Supported by National Institutes of Health grant P01AI050496. S. Favoreto and P. C. Avila are currently supported by the Ernest S. Bazley Grant to Northwestern University.
PY - 2009/6
Y1 - 2009/6
N2 - Background: Human rhinoviruses (HRVs) characteristically cause upper respiratory tract infection, but they also infect the lower airways, causing acute bronchitis and exacerbating asthma. Objective: Our purpose was to study ex vivo the differences in the response to HRV infection of nasal and bronchial epithelial cultures from the same healthy and asthmatic individuals using conditions favoring development of fully differentiated, pseudostratified mucociliary epithelium. Methods: Cells from the inferior turbinates and bronchial tree of 5 healthy and 6 asthmatic individuals were cultured at an air-liquid interface. Cultures were infected with HRV-16, and after 48 hours, the degree of infection was measured. Results: Baseline median transepithelial resistance was lower in human bronchial epithelial (HBE) cell cultures than in human nasal epithelial (HNE) cell cultures (195 Ω.cm2 [95% CI, 164-252] vs 366 Ω.cm2 [95% CI, 234-408], respectively; P < .01). Virus replicated more easily in HBE cells than in HNE cells based on virus shedding in apical wash (log tissue culture infective dose of 50%/0.1 mL = 2.0 [95% CI, 1.0-2.5] vs 0.5 [95% CI, 0.5-1.5], P < .01) and on a 20- to 30-fold greater viral load and number of infected cells in HBE cell cultures than in HNE cell cultures. The increases in expression of RANTES and double-stranded RNA-dependent protein kinase were greater in HBE cell cultures than in HNE cell cultures, as were the concentrations of IL-8, IL-1α, RANTES, and IP-10 in basolateral medium. However, no significant differences between asthmatic and healthy subjects (including IFN-β1 expression) were found. Conclusions: Differentiated nasal epithelial cells might have mechanisms of increased resistance to rhinovirus infection compared with bronchial epithelial cells. We could not confirm previous reports of increased susceptibility to HRV infection in epithelial cells from asthmatic subjects.
AB - Background: Human rhinoviruses (HRVs) characteristically cause upper respiratory tract infection, but they also infect the lower airways, causing acute bronchitis and exacerbating asthma. Objective: Our purpose was to study ex vivo the differences in the response to HRV infection of nasal and bronchial epithelial cultures from the same healthy and asthmatic individuals using conditions favoring development of fully differentiated, pseudostratified mucociliary epithelium. Methods: Cells from the inferior turbinates and bronchial tree of 5 healthy and 6 asthmatic individuals were cultured at an air-liquid interface. Cultures were infected with HRV-16, and after 48 hours, the degree of infection was measured. Results: Baseline median transepithelial resistance was lower in human bronchial epithelial (HBE) cell cultures than in human nasal epithelial (HNE) cell cultures (195 Ω.cm2 [95% CI, 164-252] vs 366 Ω.cm2 [95% CI, 234-408], respectively; P < .01). Virus replicated more easily in HBE cells than in HNE cells based on virus shedding in apical wash (log tissue culture infective dose of 50%/0.1 mL = 2.0 [95% CI, 1.0-2.5] vs 0.5 [95% CI, 0.5-1.5], P < .01) and on a 20- to 30-fold greater viral load and number of infected cells in HBE cell cultures than in HNE cell cultures. The increases in expression of RANTES and double-stranded RNA-dependent protein kinase were greater in HBE cell cultures than in HNE cell cultures, as were the concentrations of IL-8, IL-1α, RANTES, and IP-10 in basolateral medium. However, no significant differences between asthmatic and healthy subjects (including IFN-β1 expression) were found. Conclusions: Differentiated nasal epithelial cells might have mechanisms of increased resistance to rhinovirus infection compared with bronchial epithelial cells. We could not confirm previous reports of increased susceptibility to HRV infection in epithelial cells from asthmatic subjects.
KW - Human rhinovirus
KW - air-liquid interface
KW - nasal and bronchial airway epithelial cells
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U2 - 10.1016/j.jaci.2009.03.010
DO - 10.1016/j.jaci.2009.03.010
M3 - Article
C2 - 19428098
AN - SCOPUS:67649210683
SN - 0091-6749
VL - 123
SP - 1384-1390.e2
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -