African Swine Fever Virus R238L and R298L Disrupt Lung Cell's Collagen Formation and Cell Adhesion Pathway by Tar-geting Transcription Factors Containing zf-C2H2 Domain

ABSTRACT: Collagen formation pathways influence the primary structure of the extracellular ma-trix, while cell adhesion participates in the regulation of cell-cell interaction process. The collagen synthesis and degradation or cell adhesion procedure can be disrupted by viral infections, thereby playing a crucial role in virus-host interactions. The regulatory mechanisms of these two pathways during African Swine Fever Virus (ASFV) infection remain unclear. This study identified key host genes involved in the transcriptional regulation of lung tissue from ASFV-restored individuals through weighted Kendall correlation analysis of transcription factor binding sites (TFBSs) to differentially ex-pressed genes (DEGs). Among these, SP2 and KLF6 emerged as important candidate transcription factors (TFs). AFSV-host interaction prediction based on the Do-main—Domain method indicated that the R238L and R298L proteins of ASFV can target host's TFs, SP2 and KLF6. Förster resonance energy transfer assay demonstrated that ASFV’s R238L and R298L proteins can competitively bind to SP2 and KLF6’s zf-C2H2 domains. Real-time PCR demonstrated that R238L and R298L protein over-expression downregulated the SP2 and KLF6’s target genes in both HeLa and 3D4/21 cell models. During ASFV infection, SP2 regulates the collagen formation signaling pathway genes, while KLF6 modulates the expression of cell adhesion genes. Collagen matrix formation and cell adhesion profoundly influence viral infectivity, transmis-sion, and immune evasion, while also significantly impacting host immune recognition and response. The ASFV's R238L and R298L proteins, along with their target TFs SP2 and KLF6, provided clues in elucidating the pathogenesis mechanisms of ASFV infec-tion and identifying its therapeutic targets.

ORGANISM(S): Sus scrofa

PROVIDER: GSE316979 | GEO | 2026/04/01

REPOSITORIES: GEO