Reduced protein-coding transcript diversity in severe dengue emphasises the role of alternative splicing

Area of Science:

• * Molecular Biology
• * Immunology
• * Infectious Diseases

Background:

• * Dengue fever is a significant global arboviral disease.
• * Understanding host-virus interactions is crucial for managing disease severity.
• * Transcriptomic analysis offers insights into disease pathogenesis.

Purpose of the Study:

• * To analyze transcriptomic patterns in dengue patients with varying severity.
• * To identify molecular mechanisms underlying severe dengue.
• * To explore potential therapeutic targets for dengue viral pathogenesis.

Main Methods:

• * Bulk RNA sequencing (RNA-seq) was performed on 112 dengue patients.
• * Patients were stratified by disease severity.
• * Differentially expressed genes and transcript isoforms were analyzed.

Main Results:

• * Severe dengue cases showed distinct transcriptomic profiles compared to milder forms.
• * Altered splicing efficiency, indicated by retained introns and nonsense-mediated decay, was observed in severe cases.
• * Upregulated programmed cell death, haemolytic response, and impaired interferon/antiviral responses were identified.
• * The RBM39 gene was implicated in the innate immune response.

Conclusions:

• * Transcriptomic analysis reveals key differences in host response based on dengue severity.
• * Altered splicing and immune dysregulation are hallmarks of severe dengue.
• * Findings provide insights into potential therapeutic strategies and highlight the importance of sub-phenotype analysis.