猪伪狂犬病病毒感染诱导细胞衰老及其抗病毒免疫机制OA

[Objective]This study aimed to investigate the causal relationship between pseudorabies virus(PRV)infection and cellular senescence,and to analyze the regulatory effects of the cellular senescence microenvironment on viral replication,thereby providing a reference for understanding the role of cellular senescence during viral infection.[Method]After PRV infection of porcine kidney epi-thelial cells(PK-15),senescence markers and reactive oxygen species(ROS)levels were detected by β-galactosidase staining,Western blot,quantitative real-time PCR,and flow cytometry.Further-more,a stable cellular senescence model was established using doxorubicin(DOX)to evaluate the impact of this senescent state on PRV replication.[Result]PRV infection of PK-15 cells resulted in the upregulation of senescence-related indicators,indicative of the occurrence of typical virus-induced senescence(VIS).Infection of DOX-induced senescent cells with PRV revealed that the senescent microenvironment significantly suppressed PRV replication,as evidenced by reduced mRNA and pro-tein expression of viral glycoproteins gE and gB,decreased progeny virus production,and reduced viral genome copy numbers.Further analysis revealed that multiple senescence-associated secretory pheno-type(SASP)factors,including IL-6,IL-1β,TNF-α,and IL-8,were significantly upregulated in senescent cells.Treatment of normal cells with conditioned medium from senescent cells also inhibited PRV replication,indicating that SASP factors can mediate antiviral effects by paracrine manner.[Con-clusion]PRV infection induces classical VIS in PK-15 cells,and the senescent microenvironment sup-presses PRV replication through paracrine action of upregulated SASP factors,suggesting that cellular senescence represents an intrinsic host antiviral defense mechanism.