Mapping the virus-host transcriptional landscape for a better understanding of dengue disease

Despite more than 100 million infections annually and extensive scientific efforts to understand disease mechanisms, the clinical course of dengue infection, progression to severe dengue disease, particularly in children, and gender differences in outcome largely remains undefined.

By building on previous experience in RNA sequencing methodologies and analysis, we will combine bulk- and single-cell RNA sequencing with pan-dengue-specific enrichment technologies to investigate three central aims related to dengue–host interactions and virus evolution:1.

To investigate the regulatory changes and mechanisms that determine differences in clinical outcome, we will study the transcriptional response of dengue infection in patients presenting with asymptomatic, mild and severe dengue, respectively, in both primary and secondary infections.2.

By applying the same methods defined in AIM 1, we will identify gender-related differences in gene expression in relation to the clinical outcome by studying boys and girls who initially present with mild dengue fever, but who progress to severe dengue.3.

To investigate if certain dengue virus variants have different pathogenicity traits, we will, via ultra-deep sequencing of individual B-cells, characterise and quantify virus variants within individual asymptomatic, mild, severe, and patients who progress from mild to severe dengue fever. The project is expected to contribute significantly to the understanding of dengue disease mechanistic.