为探讨ADP核糖聚合酶15（ADP ribose polymerase 15, PARP15）调控S-腺苷甲硫氨酸结构域蛋白2 （S-adenosylmethionine domain protein 2, RSAD2）激活JAK-STAT信号通路影响乙型肝炎病毒（hepatitis B virus, HBV）复制的作用机制。选取2023年10月—2024年2月于贵州医科大学附属医院感染科就诊的18例HBV DNA阳性患者，以体检中心的18例健康志愿者作为阴性对照，收集受试者的临床数据和血液样本，通过体外转染构建HBV感染的细胞模型，并应用小干扰RNA和质粒分别转染细胞模型。采用GO和KEGG富集分析PARP15的富集通路，同时使用qRT-PCR和Western Blot检测PARP15信号通路相关蛋白的表达，ELISA用于检测细胞上清液中HBeAg、HBsAg的浓度。结果表明：与对照组相比，HBV阳性患者的PBMC和血清中PARP15的表达升高，而RSAD2表达降低（P<0.01）。GO和KEGG富集分析显示，PARP15参与了JAK-STAT信号通路的生物学过程。在HBV感染的细胞模型中，PARP15的表达高于对照组（P<0.01），而RSAD2则低于对照组（P<0.05）。敲低PARP15，RSAD2、STAT1和STAT2的表达增加，且HBeAg、HBsAg和HBV mRNA的表达下降（P<0.001）。过表达RSAD2，STAT1和STAT2的表达也升高，而HBeAg、HBsAg和HBV mRNA的表达降低（P<0.001）。与单独敲低PARP15或单独过表达RSAD2的细胞相比，同时敲低或同时过表达PARP15和RSAD2的细胞中，STAT1和STAT2的表达相对降低，但仍高于对照组，而HBeAg、HBsAg和HBV mRNA的表达相对升高，但仍低于对照组（P<0.05）。可见PARP15通过负向调控RSAD2，抑制JAK-STAT信号通路，从而促进HBV的复制。

In order to explore the mechanism by which ADP ribose polymerase 15 (PARP15) regulates the activation of the JAK-STAT signaling pathway by S-adenosylmethionine domain protein 2 (RSAD2) affecting the replication of hepatitis B virus (HBV). 18 HBV DNA positive patients who visited the Infection Department of Guizhou Medical University Affiliated Hospital from October 2023 to February 2024 were selected, and 18 healthy volunteers from the physical examination center were used as negative controls. Clinical data and blood samples were collected from the subjects, and an HBV infected cell model was constructed using in vitro transfection. Small interfering RNA and plasmids were transfected into the cell model, respectively. GO and KEGG enrichment were used to analyze the enrichment pathway of PARP15, while qRT PCR and Western Blot were used to detect the expression of proteins related to the PARP15 signaling pathway. ELISA was used to detect the concentrations of HBeAg and HBsAg in the cell supernatant. The results indicate that compared with the control group, the expression of PARP15 in PBMCs and serum of HBV positive patients is increased, while the expression of RSAD2 is decreases (P < 0.01). GO and KEGG enrichment analysis show that PARP15 is involved in the biological processes of the JAK-STAT signaling pathway. In the HBV infected cell model, the expression of PARP15 is higher than that of the control group (P < 0.01), while RSAD2 is lower than that of the control group (P < 0.05). Knocking down PARP15, the expression of RSAD2, STAT1, and STAT2 increase, while the expression of HBeAg, HBsAg, and HBV mRNA decrease (P <0.001). Overexpressing RSAD2, the expression of STAT1 and STAT2 also increase, while the expression of HBeAg, HBsAg, and HBV mRNA decrease (P < 0.001). Compared with cells that knocked down PARP15 alone or overexpressed RSAD2 alone, cells that knocked down or overexpressed PARP15 and RSAD2 simultaneously show a relative decrease in the expression of STAT1 and STAT2, but still higher than the control group, while the expression of HBeAg, HBsAg, and HBV mRNA is relatively upregulated but still lower than the control group (P < 0.05). It can be seen that PARP15 negatively regulates RSAD2, inhibits the JAK-STAT signaling pathway, and promotes HBV replication.