Respiratory syncytial virus infection changes the piwi-interacting RNA content of airway epithelial cells

Tiziana Corsello; Andrzej S Kudlicki; Tianshuang Liu; Antonella Casola

doi:10.3389/fmolb.2022.931354

Respiratory syncytial virus infection changes the piwi-interacting RNA content of airway epithelial cells

Front Mol Biosci. 2022 Sep 8:9:931354. doi: 10.3389/fmolb.2022.931354. eCollection 2022.

Authors

Tiziana Corsello¹, Andrzej S Kudlicki^{2

3}, Tianshuang Liu¹, Antonella Casola^{1

2

4}

Affiliations

¹ Department of Pediatrics, The University of Texas Medical Branch at Galveston (UTMB), Galveston, TX, United States.
² Institute for Translational Sciences, The University of Texas Medical Branch at Galveston (UTMB), Galveston, TX, United States.
³ Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston (UTMB), Galveston, TX, United States.
⁴ Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston (UTMB), Galveston, TX, United States.

Abstract

Piwi-interacting RNAs (piRNAs) are small non-coding RNAs (sncRNAs) of about 26-32 nucleotides in length and represent the largest class of sncRNA molecules expressed in animal cells. piRNAs have been shown to play a crucial role to safeguard the genome, maintaining genome complexity and integrity, as they suppress the insertional mutations caused by transposable elements. However, there is growing evidence for the role of piRNAs in controlling gene expression in somatic cells as well. Little is known about changes in piRNA expression and possible function occurring in response to viral infections. In this study, we investigated the piRNA expression profile, using a human piRNA microarray, in human small airway epithelial (SAE) cells infected with respiratory syncytial virus (RSV), a leading cause of acute respiratory tract infections in children. We found a time-dependent increase in piRNAs differentially expressed in RSV-infected SAE cells. We validated the top piRNAs upregulated and downregulated at 24 h post-infection by RT-qPCR and identified potential targets. We then used Gene Ontology (GO) tool to predict the biological processes of the predicted targets of the most represented piRNAs in infected cells over the time course of RSV infection. We found that the most significant groups of targets of regulated piRNAs are related to cytoskeletal or Golgi organization and nucleic acid/nucleotide binding at 15 and 24 h p.i. To identify common patterns of time-dependent responses to infection, we clustered the significantly regulated expression profiles. Each of the clusters of temporal profiles have a distinct set of potential targets of the piRNAs in the cluster Understanding changes in piRNA expression in RSV-infected airway epithelial cells will increase our knowledge of the piRNA role in viral infection and might identify novel therapeutic targets for viral lung-mediated diseases.

Keywords: RSV; airways; epithelial cells; piwi-interacting RNA; viral infection.