Tropism of Human Rhinovirus C in Lower Respiratory Tract
Refereed conference paper presented and published in conference proceedings


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AbstractRationale

Human rhinovirus (RV) is the most prevalent etiological agent that contributes to upper respiratory tract infections, the onset of wheezing and the exacerbations of asthma in children. RV-A and RV-B were described in 1956 while RV-C was discovered in 2006. The association of RV-C and the severe lower respiratory tract infection in young children has been reported. However, the available studies on rhinovirus C tropism in human respiratory tissue were limited to the upper respiratory tract. The role of RV-C in the lower airways, which is significant but not available in the field, warrants a systematic investigation.

Method

Different genotypes of RV-C were isolated and established in our CDHR3-529Y expressing H1-HeLa cell. They were isolated from nasopharyngeal specimens of hospitalized children aged < 17 years old with the clinical diagnosis of asthma exacerbations, upper respiratory tract infections or pneumonia and from asymptomatic children from community-based surveillance. The infectious RV-C stocks were quantified using plaque assay and the whole genome sequencing was performed.

The tissue tropism was studied by inoculating these RV-Cs with a RV-A16 control into the human respiratory organ cultures of the nasopharynx, bronchus, and lung. In addition, the human primary type I-like pneumocyte was used as the in-vitro model to address the replication of RV-C with a defined multiplicity-of-infection.

The infected cultures were monitored from 1 to 96 hour-post-infection and the supernatant were harvested for viral titration to construct the replication kinetics. The cellular tropism was determined by the co-expression of cellular markers and viral protein. Antibodies specific to ciliated cell (beta-tubulin), goblet cell (MUC5AC), basal cell (p63/krt5), club cell (SCGB1A1), type-I pneumocyte (podoplanin) and type-II pneumocyte (surfactant protein C) were used to identify the infected cell type.

Results

The replication of RVs peaked at 96 hour-post-inoculation. The human bronchial tissue supported a higher replication of RV-A16 when compared to RV-Cs. Not every tested genotype of RV-C could replicate in the bronchial tissue, though the cadherin-related family member 3 was present. RV-C41 and RV-23 replicated better in the ex-vivo culture of human lung snippets and in the in-vitro culture of primary human type I-like pneumocytes, respectively, when compared to RV-A16.

Conclusion

The lung tropism of RV-Cs might contribute to its association to severe lung infection. The cellular tropism, especially in those "progenitor cell populations", e.g. basal cell, club cell and type II pneumocyte, would be of immense interest in the pathogenesis of RV infection and airways remodeling.
All Author(s) ListChan RWY, Tao KP, JGS Tsun, WY Yu, H Wang, YP Song, MCF Tong, CSH Ng, PKS Chan, WM Lee, TF Leung
Name of ConferenceAmerican Thoracic Society 2017 International Conference
Start Date of Conference19/05/2017
End Date of Conference24/05/2017
Place of ConferenceWashington, DC
Country/Region of ConferenceUnited States of America
Proceedings TitleAmerican Journal of Respiratory and Critical Care Medicine
Year2017
Volume Number195
PagesA5307 - A5307
ISSN1073-449X
eISSN1535-4970
LanguagesEnglish-United Kingdom
KeywordsRhinovirus C, Human respiratory organ culture, tropism

Last updated on 2020-18-10 at 02:40