Asian Zika Virus Isolate Significantly Changes the Transcriptional Profile and Alternative RNA Splicing Events in a...

Area of Science:

• Molecular Virology
• Transcriptomics
• RNA Biology

Background:

• Alternative splicing (AS) generates protein diversity from a single gene.
• Viruses are known to manipulate host cell machinery, including splicing.
• The global impact of viral infections on the alternative splicing landscape is not well understood.

Purpose of the Study:

• To investigate the effects of Zika virus (ZIKV) and dengue virus (DENV) infection on the alternative splicing profiles of neuronal cells.
• To compare the impact of different ZIKV strains (Puerto Rican ZIKV^PR vs. Ugandan ZIKV^MR) and DENV serotype 2 (DENV2) on host cell transcription and splicing.

Main Methods:

• Infection of neuronal cells with ZIKV^PR, ZIKV^MR, and DENV2.
• Transcriptome-wide analysis to assess differential gene expression.
• Alternative splicing event analysis and gene ontology enrichment.

Main Results:

• ZIKV^PR induced significantly more differential gene expression changes than ZIKV^MR or DENV2, despite similar viral RNA levels and infectivity.
• ZIKV^PR triggered a greater number of alternative splicing events compared to ZIKV^MR or DENV2.
• Gene ontology analysis revealed enrichment of splicing-related genes among those affected by alternative splicing changes.

Conclusions:

• Zika virus infection disrupts cellular RNA homeostasis at both transcriptional and alternative splicing levels.
• ZIKV^PR exhibits a more profound impact on the host cell's splicing landscape than ZIKV^MR or DENV2.
• These findings offer molecular insights into the neuropathologies associated with Zika virus infection.