Investigating roles of RNA editing in virus host interaction

Publication Type:
Thesis
Issue Date:
2024
Full metadata record
The losses incurred during the COVID-19 pandemic underscore the urgent need to study host adaptations of emerging pathogens and their life cycles. The virus infection cycle comprises several key steps, including virus entry and gene expression, both crucial for understanding host adaptation. This thesis focuses on these processes, particularly the role of RNA editing in viral infections. RNA editing, catalysed by ADAR and ADAT enzymes, modifies viral mRNA and host tRNA, influencing multiple aspects of viral gene expression. Statistical analysis of codon usage biases between human and non-human viruses revealed usage differences associated with ADAR and ADAT editing. Machine learning models, using mainly Relative Synonymous Codon Usage (RSCU) features, successfully predicted virus-host relationships, generating a virus codon fitness (VCF) score to assess codon fitness in hosts. These findings demonstrate the potential of machine learning in predicting host adaptation of emerging viruses. Virus entry depends on protein-protein interactions (PPI) between viral Spike proteins and host receptors. A newly developed FRET-based assay detected interactions between SARS-CoV-2 Spike and human ACE2/TMPRSS2. Additionally, RNA sequencing identified RNA editing events in these receptors, suggesting potential regulatory mechanisms in virus entry. These insights enhance our understanding of viral adaptation and offer predictive tools for emerging pathogens.
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