Host cell transcriptome profile during wild-type and attenuated dengue virus infection

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Dengue viruses (DENV1-4) hijack host cell machinery for replication.
• Host responses, including gene expression changes, are crucial during DENV infection.
• Regulation of host gene function via transcriptional start site (TSS) selection and RNA post-transcriptional modifications is unexplored in DENV infection.

Purpose of the Study:

• To investigate novel transcript variations in the human host in response to DENV infection.
• To explore the roles of TSS selection and RNA post-transcriptional modifications in the host response to DENV.
• To compare host transcriptome responses to pathogenic DENV1 and its attenuated derivative.

Main Methods:

• RNA sequencing (RNAseq) was employed to analyze host transcript variations.
• RNAseq was used to identify novel transcript isoforms and splice variants.
• Differential gene expression analysis was performed comparing wild-type DENV1 and attenuated DENV1 infections.

Main Results:

• Extensive, previously uncharacterized TSS and post-transcriptional RNA modifications were identified in response to DENV infection.
• Many differentially expressed genes are known to be essential for flavivirus propagation or interact with DENV proteins.
• Significant differences were observed in the human transcriptome response to wild-type DENV versus attenuated DENV infection.

Conclusions:

• DENV infection induces widespread, uncharacterized transcriptomic alterations in the host.
• Alternative RNA processing events may constitute an innate immune response against DENV.
• Wild-type DENV appears to evade this RNA processing-mediated innate immune response more effectively than attenuated strains.