Using genetics and cell models to understand virus-host interactions in the airways

Shrees, Christina

Using genetics and cell models to understand virus-host interactions in the airways

Publication Date

July 31, 2026

Creator

Shrees, Christina

University of Nottingham

Abstract

Respiratory virus infections are a major cause of mortality and morbidity worldwide. It is important to investigate the genetic and molecular background underlying host-virus interactions. Identifying genes and pathways that may modify viral pathogenesis could facilitate the development of therapeutics to treat viral infections. Three approaches were used in the thesis to understand host-virus interactions: genomics, transcriptomics and cell models. Signal-to-gene association analysis was conducted to translate genetic signals associated with susceptibility or severity to rhinovirus (RV), respiratory syncytial virus (RSV), and SARS-CoV-2 infection. 6, 108 and 119 candidate causal genes were identified for RV, RSV and SARS-CoV-2 respectively. IL6-, IL-AS1 and STEAP1B was found to overlap between the three viruses. Downstream analysis of the genes revealed that immunomodulatory pathways such as the Th1 signalling pathway may be particularly important for the three viruses. Drugs currently in Phase I, II and III of clinical trials which target the candidate causal genes were identified. Transcriptomics was utilised to investigate how human bronchial epithelial cells (HBECs) respond to prolonged RSV-A2 and RV-A16 infection. Cell cycle pathways were predicted to be activated upon prolonged RSV infection whereas inflammatory pathways were predicted to be downregulated. Keratinisation was the top pathway predicted to be activated whereas elastic fibre formation pathway was predicted to be downregulated in prolonged RV-A16 infection. To further understand host-virus interaction, induced pluripotent stem cell (iPSC) and HBEC air-liquid interface models of the airway epithelium were used to study RSV infection. Overall, these findings provide insight into genes and pathways important for host-virus susceptibility, and opportunities for development of therapeutics.

Item Type

ethesis

Thesis Type

PhD

Supervisors

Sayers, Ian