Effect of CSFV on Differential Genes of Histone Lactylation at H3K18 in the PI3K-AKT Signaling Pathway

Zhang, H.; Han, Z.; Zhao, X.; Zhu, J.; Shao, N.; Sun, K.; Li, W.; Yao, Y.; Liang, X.; Yang, M.; Gao, Y.; Chen, J.; Liang, Y.; Liu, Q.; Li, X.; Cao, Z.

doi:10.64898/2026.06.26.734696

bioRxiv · 10.64898/2026.06.26.734696

Effect of CSFV on Differential Genes of Histone Lactylation at H3K18 in the PI3K-AKT Signaling Pathway

Zhang, H.·Han, Z.·Zhao, X.·Zhu, J.·Shao, N.·Sun, K.·Li, W.·Yao, Y.·Liang, X.·Yang, M.·Gao, Y.·Chen, J.·Liang, Y.·Liu, Q.·Li, X.·Cao, Z.

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Abstract

Classical swine fever (CSF) is a highly contagious disease caused by Classical swine fever virus (CSFV), posing a serious threat to the global swine industry. This study aimed to investigate the effect of CSFV on differential genes of histone lactylation at the H3K18 site in the PI3K-AKT signaling pathway. The site with the most significant change in histone lactylation antibody level was screened by Western blot. Omics analysis was performed using CUT&Tag technology to identify differential genes in the PI3K-AKT pathway between the CSFV-infected group and the mock group, followed by validation using RT-qPCR. Functional analysis of significantly differential proteins was conducted, and the protein expression level of THBS4 was detected by Western blot. The results showed that after CSFV infection of 3D4/21 cells, the H3K18la site exhibited the most significant difference in antibody level. A total of 8,859 differential genes at the H3K18la site were identified by CUT&Tag analysis, including 6,349 up-regulated genes and 2,510 down-regulated genes. Further focusing on the PI3K-AKT signaling pathway, 10 differential genes were identified, comprising 6 up-regulated genes and 4 down-regulated genes. Compared with the control group, the mRNA expression levels of CD19, LAMA1, PDGFRA, BDNF, ANGPT4, and THBS4 were up-regulated in the CSFV-infected group, while FOXO3 and NRTN were down-regulated. Western blot results showed that the protein expression level of THBS4 increased after CSFV infection. These findings lay an important foundation for understanding the molecular mechanisms regulating viral replication and immune evasion, and have significant scientific implications and potential application value.

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Zhang, H., Han, Z., Zhao, X., Zhu, J., Shao, N., Sun, K., Li, W., Yao, Y., Liang, X., Yang, M., Gao, Y., Chen, J., Liang, Y., Liu, Q., Li, X., Cao, Z.. 2026-06-29. Effect of CSFV on Differential Genes of Histone Lactylation at H3K18 in the PI3K-AKT Signaling Pathway. https://doi.org/10.64898/2026.06.26.734696

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