Rhinovirus C targets ciliated airway epithelial cells.

Autor: Griggs TF; Department of Pediatrics, School of Medicine and Public Health, CSC K4/945, 600 Highland Ave, Madison, 53792, WI, USA. tgriggs@wisc.edu.; Cellular & Molecular Pathology Graduate Program, Madison, WI, USA. tgriggs@wisc.edu.; Medical Scientist Training Program, Madison, WI, USA. tgriggs@wisc.edu., Bochkov YA; Department of Pediatrics, School of Medicine and Public Health, CSC K4/945, 600 Highland Ave, Madison, 53792, WI, USA., Basnet S; Department of Pediatrics, School of Medicine and Public Health, CSC K4/945, 600 Highland Ave, Madison, 53792, WI, USA., Pasic TR; Department of Surgery, School of Medicine and Public Health, Madison, WI, USA., Brockman-Schneider RA; Department of Pediatrics, School of Medicine and Public Health, CSC K4/945, 600 Highland Ave, Madison, 53792, WI, USA., Palmenberg AC; Institute for Molecular Virology, University of Wisconsin, Madison, WI, USA., Gern JE; Department of Pediatrics, School of Medicine and Public Health, CSC K4/945, 600 Highland Ave, Madison, 53792, WI, USA.; Cellular & Molecular Pathology Graduate Program, Madison, WI, USA.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2017 May 04; Vol. 18 (1), pp. 84. Date of Electronic Publication: 2017 May 04.
DOI: 10.1186/s12931-017-0567-0
Abstrakt: Background: The Rhinovirus C (RV-C), first identified in 2006, produce high symptom burdens in children and asthmatics, however, their primary target host cell in the airways remains unknown. Our primary hypotheses were that RV-C target ciliated airway epithelial cells (AECs), and that cell specificity is determined by restricted and high expression of the only known RV-C cell-entry factor, cadherin related family member 3 (CDHR3).
Methods: RV-C15 (C15) infection in differentiated human bronchial epithelial cell (HBEC) cultures was assessed using immunofluorescent and time-lapse epifluorescent imaging. Morphology of C15-infected differentiated AECs was assessed by immunohistochemistry.
Results: C15 produced a scattered pattern of infection, and infected cells were shed from the epithelium. The percentage of cells infected with C15 varied from 1.4 to 14.7% depending on cell culture conditions. Infected cells had increased staining for markers of ciliated cells (acetylated-alpha-tubulin [aat], p < 0.001) but not markers of goblet cells (wheat germ agglutinin or Muc5AC, p = ns). CDHR3 expression was increased on ciliated epithelial cells, but not other epithelial cells (p < 0.01). C15 infection caused a 27.4% reduction of ciliated cells expressing CDHR3 (p < 0.01). During differentiation of AECs, CDHR3 expression progressively increased and correlated with both RV-C binding and replication.
Conclusions: The RV-C only replicate in ciliated AECs in vitro, leading to infected cell shedding. CDHR3 expression positively correlates with RV-C binding and replication, and is largely confined to ciliated AECs. Our data imply that factors regulating differentiation and CDHR3 production may be important determinants of RV-C illness severity.
Databáze: MEDLINE
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