Transcriptomic Signatures of Zika Virus Infection in Patients and a Cell Culture Model

Area of Science:

• Virology
• Molecular Biology
• Genomics

Background:

• Zika virus (ZIKV) causes severe neurological and developmental issues, especially in infants infected prenatally.
• Understanding ZIKV's molecular pathology is crucial, yet studies often lack integrated analysis of patient and cell culture data.
• Transcriptome-wide studies are vital for dissecting ZIKV's impact on host gene expression.

Purpose of the Study:

• To investigate the utility of cell culture models in replicating molecular changes observed in ZIKV-infected patients.
• To compare transcriptional and alternative splicing profiles between ZIKV-infected A549 cells and patient-derived peripheral blood mononuclear cells (PBMCs).
• To establish a foundation for future research on ZIKV's molecular mechanisms, including alternative splicing.

Main Methods:

• RNA sequencing (RNA-seq) analysis was performed on ZIKV-infected human lung adenocarcinoma A549 cells.
• Transcriptional and alternative splicing profiles were compared with previously published RNA-seq data from pediatric patients at different ZIKV infection phases (early acute, late acute, convalescent).
• Comparative analysis focused on identifying overlapping molecular changes between the cell culture model and patient samples.

Main Results:

• ZIKV infection in A549 cells recapitulated key transcriptional alterations observed in PBMCs from ZIKV-infected pediatric patients.
• The overlap in alternative splicing profiles between cell culture and patient samples was less pronounced than the transcriptional overlap.
• A549 cell cultures effectively mirrored specific molecular responses to ZIKV infection found in human patients.

Conclusions:

• Cell culture models, such as A549 cells, are valuable tools for studying select molecular changes associated with ZIKV infection in patients.
• The findings support the use of cell culture systems for dissecting ZIKV's impact on host gene expression.
• This study lays the groundwork for future investigations into the role of alternative splicing in ZIKV pathogenesis.