Porcine reproductive and respiratory syndrome (PRRS) is an important infectious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV),leading to significant economic losses in swine industry worldwide.Although several studies have shown that PRRSV can affect the cell cycle of infected cells,it is still unclear how it manipulates the cell cycle to facilitate its proliferation.In this study,we analyzed the mRNA expression profiles of transcription factors in PRRSV-infected 3D4/21 cells by RNA-sequencing.The result shows that the expression of transcription factor DP2(TFDP2) is remarkably upregulated in PRRSV-infected cells.Further studies show that TFDP2 contributes to PRRSV proliferation and the PRRSV nucleocapsid (N) protein induces TFDP2 expression by activating C/EBPβ.TFDP2 positively regulates cyclin A expression and triggers a less proportion of cells in the S phase,which contributes to PRRSV prolif-eration.This study proposes a novel mechanism by which PRRSV utilizes host protein to regulate the cell cycle to favor its infection.Findings from this study will help us for a better understanding of PRRSV pathogenesis.