Oncotarget

Research Papers:

A pilot study on primary cultures of human respiratory tract epithelial cells to predict patients’ responses to H7N9 infection

Chung-Guei Huang, Li-Ang Lee, Yi-Cheng Wu, Mei-Jen Hsiao, Jim-Tong Horng, Rei-Lin Kuo, Chih-Heng Huang, Ya-Chu Lin, Kuo-Chien Tsao, Min-Chi Chen, Tse-Ching Chen and Shin-Ru Shih _

PDF  |  HTML  |  How to cite

Oncotarget. 2018; 9:14492-14508. https://doi.org/10.18632/oncotarget.24537

Metrics: PDF 1377 views  |   HTML 2847 views  |   ?  


Abstract

Chung-Guei Huang1,2,3,*, Li-Ang Lee4,5,*, Yi-Cheng Wu5,6, Mei-Jen Hsiao1,3, Jim-Tong Horng1,7, Rei-Lin Kuo1,2, Chih-Heng Huang1,8, Ya-Chu Lin3, Kuo-Chien Tsao1,3, Min-Chi Chen5,9, Tse-Ching Chen5,10 and Shin-Ru Shih1,2,3

1Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan 33302, Taiwan, ROC

2Graduate Institute of Biomedical Sciences, Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC

3Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC

4Department of Otorhinolaryngology - Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan, ROC

5Faculty of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC

6Department of Surgery, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan, ROC

7Graduate Institute of Biomedical Sciences, Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan, ROC

8Institute of Preventive Medicine, National Defense Medical Center, Taipei 11490, Taiwan, ROC

9Department of Public Health and Biostatistics Consulting Center, Chang Gung University, Taoyuan 33302, Taiwan, ROC

10Department of Pathology, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan, ROC

*These authors have contributed equally to this work

Correspondence to:

Shin-Ru Shih, email: [email protected]

Tse-Ching Chen, email: [email protected]

Keywords: avian influenza A(H7N9) virus; primary epithelial cells; tropism; cytokine; patient-related characteristics

Received: September 01, 2017     Accepted: February 10, 2018     Epub: February 20, 2018    Published: March 06, 2018

ABSTRACT

Avian influenza A(H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. We aimed to investigate whether primary cultures of human respiratory tract epithelial cells are helpful to understand H7N9 virus pathogenesis and tissue tropism, and to evaluate how patient-related characteristics can affect the host’s response to infection. Normal human bronchial epithelial cells (isolated from two different donors) and primary epithelial cells (harvested from 27 patients undergoing airway surgery) were experimentally infected with H7N9 and/or H1N1pdm for 72 h. After virus infection, the culture media were collected for viral RNA quantitation and cytokine detection. Both H7N9 and H1N1pdm viruses replicated and induced a cytokine response differently for each donor in the normal human bronchial epithelial model. H7N9 replicated equivalently in epithelial cells harvested from the inferior turbinate and paranasal sinus, and those from the larynx and bronchus, at 72 h post-infection. Viral RNA quantity at 72 h was significantly higher in patients aged 21–64 years than in patients aged ≥ 65 years; however, no effects of sex, medical comorbidities, and obesity were noted. H7N9-infected cultured cells released multiple cytokines within 72 h. Levels of interleukin-1β, interleukin-6, interleukin-8, interferon-γ, and tumor necrosis factor-α were associated differently with patient-related characteristics (such as age, sex, obesity, and medical comorbidities). In the era of precision medicine, these findings illustrate the potential utility of this primary culture approach to predict a host’s response to H7N9 infection or to future infection by newly emerging viral infections, and to dissect viral pathogenesis.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 24537