Screening core genes and signaling pathways after SFTSV infection by integrated transcriptome profiling analysis

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Severe fever with thrombocytopenia syndrome virus (SFTSV) causes severe fever with thrombocytopenia syndrome (SFTS), a disease with high mortality and rapid global spread.
• The precise mechanisms underlying SFTSV pathogenesis and its impact on host cells remain largely undetermined.

Purpose of the Study:

• To investigate the host cell's transcriptional response to SFTSV infection.
• To elucidate the molecular mechanisms by which SFTSV induces disease symptoms, particularly thrombocytopenia.

Main Methods:

• High-throughput RNA sequencing (RNA-Seq) was employed to analyze gene expression profiles in HEK 293 cells infected with SFTSV over four time points (6, 12, 24, and 48 hours).
• Differential gene expression analysis was performed to identify key genes and pathways affected by the viral infection.

Main Results:

• A significant number of differentially expressed genes (DEGs) were identified, with counts increasing over time post-infection (115 at 6h, 191 at 12h, 259 at 24h, and 660 at 48h).
• SFTSV infection upregulated genes involved in cytokine-related inflammatory pathways (e.g., TNF, CXCL1, CXCL8, CCL20), indicating a robust host inflammatory response.
• Genes essential for platelet activation (GNA13, ARHGEF12, RHOA, ROCK1, MYL12A) were downregulated, suggesting a potential mechanism for SFTSV-induced thrombocytopenia.

Conclusions:

• SFTSV infection elicits a strong inflammatory response characterized by the induction of cytokine-related gene expression.
• The downregulation of platelet activation pathway genes provides a molecular basis for the thrombocytopenia observed in SFTS patients.
• This research enhances the understanding of the complex interactions between SFTSV and the host, paving the way for future therapeutic strategies.