阻断Wee1激酶诱导有丝分裂灾难以抑制猪圆环病毒2型复制OA

Porcine circovirus type 2(PCV2)is the primary pathogen of porcine circovirus-associated diseases,posing a serious threat to the global swine industry.This study aimed to evaluate the effect of targeting the host cell cycle regulator Wee1 kinase on PCV2 replication.Using an in vitro infection model,we systematically analyzed the impact of PCV2 infection on the host DNA damage response(DDR)and cell cycle progression through a chromosome spread assay,indirect immunofluorescence assay,and Western blotting analyses,and assessed the antiviral activity of the Wee1 inhibitor MK-1775.The results showed that PCV2 infection significantly activated host DDR,with 84%of infected cells exhibiting γ-H2AX positivity,and induced cell cycle arrest in the S phase.Further analysis revealed that MK-1775 treatment triggered mitotic catastrophe in approximately 60%of infected cells,accompanied by a significant reduction in the PCV2 infection rate and viral protein expression levels.These findings indicate that PCV2 replication relies on host cell cycle regulation,and that Wee1 inhibition effectively suppresses viral replication by disrupting cell cycle checkpoints and inducing mitotic catastrophe.Thus,targeting the host cell cycle regulator Wee1 may represent a potential strategy for intervening in PCV2 infection.