Introduction

Coronaviruses (CoVs) pose a major risk to human health, exemplified by the emergence of SARS-CoV-2 and COVID-19. During infection, viruses depend on host factors for replication, while cellular mechanisms act to restrict infection. Non-coding RNAs (ncRNAs) are increasingly recognized as key regulators of cellular processes. Studying host long ncRNAs (lncRNAs) during infection may reveal novel virus–host interactions and potential therapeutic targets.

Objectives

We aim to elucidate the role of host lncRNAs during CoV infection to enable the identification of new targets for pharmaceutical intervention. In more detail, this project aims to identify, functionally validate and characterize lncRNAs to dissect their role during CoV replication.

Materials and methods

To identify lncRNAs involved in host cellular responses, human airway epithelial cells (hAEC) were either challenged with SARS-CoV-2 or treated with IFN-α or IFN-λ. We performed a microarray screen and conducted bioinformatic analysis to identify dysregulated lncRNAs following treatment. To validate the identified lncRNAs, their expression was altered using siRNA-mediated knockdown. Cells were then challenged with CoVs to assess the impact on viral replication.

Results

Bioinformatic analysis revealed differential expression of lncRNAs between the different treatment regimens. IFN-α treatment induced significant changes in a large number of lncRNAs, whereas IFN-λ resulted in significantly less dysregulation. Following CoV infection, few lncRNAs were differentially expressed at 16hpi, with GO analysis linking down-regulated lncRNAs to autophagy. At 72hpi, an increased number of lncRNAs was dysregulated, with pathways associated with the immune response. First results point towards reduced viral replication upon knockdown of specific lncRNAs, suggesting functional relevance.

Conclusions

We were able to demonstrate altered lncRNA expression upon IFN stimulation and viral infection. GO analysis implicated a potential role of lncRNAs during CoV immune control. Future studies will functionally characterize specific lncRNAs during virus replication and immune regulation, offering new therapeutic strategies.