Repetitive HRV-16 infection changes the transcriptome and epigenome in the airway epithelium

Background: Recurrent human rhinovirus (HRV) infection in early life has been associated with asthma development later in life. The airway epithelium initiates innate immune responses and undergoes epigenetic reprogramming upon HRV infection. I hypothesize that repetitive HRV infection trains an aberrantly amplified innate immune response in the airway epithelial cells.

Results: Primary normal human bronchial epithelial cells (NHBEs) were infected with HRV-16 repetitively and then exposed to IL-13 at the air-liquid interface (ALI). Repetitive HRV-16 infected cells had an enhanced mRNA expression of RIG-1 and CXCL10 and increased protein production of CXCL10, IFNʎ1, IL-8, IL-4 and IL-5 in response to IL-13 exposure. Single-cell RNA sequencing (scRNA-seq) identified several anti-viral genes, such as IFI27, IFI44, ISG15, that were upregulated by HRV-16 in epithelial ciliated and club cells. In addition, scRNA-seq revealed an enhanced expression of RIG-1, ISG20 and CXCL10 in repetitive HRV-16 infected ciliated cells upon IL-13 exposure. Gene KRT6A (a IL-13-responsive DEG) was highly expressed following IL-13 exposure in the repetitive HRV-16 infected club and goblet cells. Furthermore, repetitive HRV-16 infection altered the genome-wide DNA methylation profile of NHBE cells and changed methylation levels at gene CXCL10, IL-4 and IL-5.

Conclusion: Repetitive HRV-16 infection could train an enhanced inflammatory response in the airway epithelial cells. scRNA-seq has demonstrated the importance of airway epithelial ciliated and club cells in mediating the anti-viral responses against HRV-16, and it also suggested that repeated HRV-16 infection trains an enhanced interferon response in the ciliated cells and primes for amplified IL-13-induced inflammation in the club and goblet cells. Furthermore, repetitive HRV-16 infection alters the DNA methylation profile and changes the methylation level of the trained genes.


Use and reproduction:

No license. The provisions of the German Copyright Act (UrhG) apply.

Please note that individual components of the publication may be subject to other licensing or copyright conditions.


Citation style:
Could not load citation form.