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

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.