Beta-Sitosterol Enhances Classical Swine Fever Virus Infection: Insights from RNA-Seq Analysis

TL;DR

This study shows that beta-sitosterol boosts Classical Swine Fever Virus replication in cells and identifies related gene changes.

Contribution

The novel finding is that beta-sitosterol enhances CSFV replication by modulating the NF-κB pathway through IκBα suppression.

Findings

Beta-sitosterol significantly enhances replication of CSFV-Shimen and C-strain in PK-15 cells.

RNA-Seq analysis reveals 175 differentially expressed genes after BS exposure.

Suppression of IκBα by BS activates the NF-κB pathway and promotes CSFV replication.

Abstract

Beta-sitosterol (BS), a naturally occurring phytosterol abundant in plants, has been reported to exhibit diverse biological activities, including immunomodulatory and antiviral effects. Classical swine fever virus (CSFV), a member of the Pestivirus genus, remains a persistent threat to the swine industry worldwide, causing considerable economic damage. Our research found that BS significantly enhances the replication of both the CSFV-Shimen strain and the attenuated C-strain vaccine virus in PK-15 cells. Additionally, transcriptomic profiling (RNA-Seq) identified 175 differentially expressed genes (DEGs) following BS exposure, comprising 53 upregulated and 122 downregulated genes. Further results demonstrated that treatment with β-sitosterol suppressed IκBα expression, thereby activating the NF-κB pathway, and that knockdown of endogenous IκBα significantly promoted CSFV replication. These findings contribute to a deeper understanding of how BS influences the CSFV infection process, suggesting its role as a host lipid-associated factor facilitating viral propagation.

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