Comparative Transcriptomic Analysis of Rhinovirus and Influenza Virus Infection

Thrimendra Kaushika Dissanayake; Sascha Schäuble; Mohammad Hassan Mirhakkak; Wai-Lan Wu; Anthony Chin-Ki Ng; Cyril C Y Yip; Albert García López; Thomas Wolf; Man-Lung Yeung; Kwok-Hung Chan; Kwok-Yung Yuen; Gianni Panagiotou; Kelvin Kai-Wang To

doi:10.3389/fmicb.2020.01580

Comparative Transcriptomic Analysis of Rhinovirus and Influenza Virus Infection

Front Microbiol. 2020 Jul 21:11:1580. doi: 10.3389/fmicb.2020.01580. eCollection 2020.

Authors

Thrimendra Kaushika Dissanayake¹, Sascha Schäuble², Mohammad Hassan Mirhakkak², Wai-Lan Wu¹, Anthony Chin-Ki Ng¹, Cyril C Y Yip¹, Albert García López², Thomas Wolf², Man-Lung Yeung^{1

3

4

5}, Kwok-Hung Chan¹, Kwok-Yung Yuen^{1

3

4

5}, Gianni Panagiotou^{2

6}, Kelvin Kai-Wang To^{1

3

4

5}

Affiliations

¹ Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
² Systems Biology and Bioinformatics Unit, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Jena, Germany.
³ State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
⁴ Department of Clinical Microbiology and Infection Control, The University of Hong Kong, Hong Kong, China.
⁵ Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China.
⁶ Systems Biology and Bioinformatics Group, School of Biological Sciences, Faculty of Sciences, The University of Hong Kong, Hong Kong, China.

Abstract

Rhinovirus (RV) and influenza virus are the most frequently detected respiratory viruses among adult patients with community acquired pneumonia. Previous clinical studies have identified major differences in the clinical presentations and inflammatory or immune response during these infections. A systematic transcriptomic analysis directly comparing influenza and RV is lacking. Here, we sought to compare the transcriptomic response to these viral infections. Human airway epithelial Calu-3 cells were infected with contemporary clinical isolates of RV, influenza A virus (IAV), or influenza B virus (IBV). Host gene expression was determined using RNA-seq. Differentially expressed genes (DEGs) with respect to mock-infected cells were identified using the overlapping gene-set of four different statistical models. Transcriptomic analysis showed that RV-infected cells have a more blunted host response with fewer DEGs than IAV or IBV-infected cells. IFNL1 and CXCL10 were among the most upregulated DEGs during RV, IAV, and IBV infection. Other DEGs that were highly expressed for all 3 viruses were mainly genes related to type I or type III interferons (RSAD2, IDO1) and chemokines (CXCL11). Notably, ICAM5, a known receptor for enterovirus D68, was highly expressed during RV infection only. Gene Set Enrichment Analysis (GSEA) confirmed that pathways associated with interferon response, innate immunity, or regulation of inflammatory response, were most perturbed for all three viruses. Network analysis showed that steroid-related pathways were enriched. Taken together, our data using contemporary virus strains suggests that genes related to interferon and chemokine predominated the host response associated with RV, IAV, and IBV infection. Several highly expressed genes, especially ICAM5 which is preferentially-induced during RV infection, deserve further investigation.

Keywords: ICAM5; cytokines; influenza; interferons; rhinovirus; transcriptomics analysis.