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1、The effects of coronavirus on human nasal ciliated respiratory epithelium M.A. Chilvers*, M. McKean*, A. Rutman*, B.S. Myint#, M. Silverman*, C. O9Callaghan* The effects of coronavirus on human nasal ciliated respiratory epithelium. M.A. Chilvers, M. McKean, A. Rutman, B.S. Myint, M. Silverman, C. O
2、9Callaghan. #ERS Journals Ltd 2001. ABSTRACT: Human coronavirus (HCoV) accounts for 1530% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium. The authors examined the effects of infection with HCoV on
3、ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immedi- ately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the
4、 inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by trans- mission electron microscopy. Symptom diaries were kept for
5、 the duration of the study. All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz
6、 (95% confi dence interval (CI): 8.614.0) and day 3 (9.4 Hz (95% CI 7.211.6), there was a signifi cant increase (pv0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 00.5) and day 3 (1.1 (95% CI 0.51.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary stru
7、cture and function were found between day 0 and day 3. Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infectio
8、n, may occur without overt clinical symptoms. Eur Respir J 2001; 18: 965970. *Childrens Asthma Centre, Dept of Child Health, University of Leicester, Leicester Royal Infi rmary, and #Dept ofMicrobiologyandImmunology, University of Leicester, Leicester, UK. Correspondence:C.O9Callaghan, Childrens Ast
9、hma Centre, Dept of Child Health, University of Leicester, RobertKilpatrickClinicalSciences Building, Leicester Royal Infi rmary, 6694, P.O. Box 65, Leicester LE2 7LX, UK. Fax: 44 1162523282 Keywords: Cilia ciliary beat frequency coronavirus respiratory epithelium ultrastructure viral infection Rece
10、ived: October 26 2000 Accepted after revision June 1 2001 ThisworkwassupportedbyThe Cystic Fibrosis Trust, Masons Medical Foundation and The National Asthma Campaign. The common cold is a universally recognized short illness, in which the main symptoms involve the upper respiratory tract and in whic
11、h nasal symptoms usually predominate. Understanding the interaction between virus and epithelium is an important step in determining the mechanisms by which symptoms are produced. Structural damage to the respiratory epithelium 13 and abnormal ciliary function 1, 4, 5 during viral infection may disr
12、upt the mucociliary escalator 4, 6, contributing to symptoms of nasal discharge and obstruction. Although some infected volunteers suffer nasal congestion and discharge, an equal number of infected subjects have no defi nite symptoms. The reasons for this are still unclear 7. Human coronaviruses (HC
13、oV) are the second most prevalent cause of the common cold. They account for 1530% of proven viral infections 8 and may cause exacerbation of lower respiratory diseases such as asthma 9. Data on the effect of HCoV infec- tion of the respiratory epithelium are surprisingly sparse. The initial method
14、for identifying HCoV used in vitro tracheal organ cultures, in which infection was detected with diffi culty. Microscopy of light refl ected from the epithelial surface was used as an indicator of ciliary activity, with loss of the light refl ection taken as the outcome measure for viral infection 1
15、0. Other data include an incidental fi nding, on electron micro- scopy, of HCoV infection in a 2-yr-old female being investigated for ciliary dyskinesia. It is of interest that this infection was asymptomatic with no signs of a common cold at the time of biopsy or afterwards 11. In the present study
16、, HCoV 229E (American Type Culture Collection, Rockville, MD, USA), one of the two major serotypes of coronavirus accounting for upper respiratory tract infections 12, was used to inoculate healthy volunteers. The aim was to determine the effect of HCoV infection on the ultra- structure of nasal epithelium and on the beat fre- quency and beat pattern of nasal cilia. Methods Subjects Fifteen adult volunteers (11 males, four females) without nasal or respiratory disease were recruited. Ages rang
