Bacteriophages (phages) are viruses of bacteria. Despite the growing progress in research on phage interactions with eukaryotic cells, our understanding of the roles of phages and their potential implications remains incomplete. The objective of this study was to investigate the effects of the Staphylococcus aureus phage vB_SauM_JS25 on murine norovirus (MNV) replication. Experiments were performed using the RAW 264.7 cell line. After phage treatment, MNV multiplication was significantly inhibited, as indicated by real-time quantitative polymerase chain reaction (RT-qPCR) analysis, western blotting, the 50% tissue culture infectious dose and immunofluorescence. Furthermore, we revealed transcriptional changes in phage/MNV co-incubated RAW 264.7 cells through RNA sequencing (RNA-seq) and bioinformatic analysis. Our subsequent analyses revealed that the innate immune response might play an important role in restriction of MNV replication, such as the cellular response to IFN-γ and response to IFN-γ. Additionally, gene expression of IL-10, Arg-1, Ccl22, GBP2, GBP3, GBP5, and GBP7 was increased significantly, which indicated a strong correlation between RT-qPCR and RNA-seq results. Furthermore, phage treatment activated guanylate binding proteins (GBPs), as revealed by RT-qPCR analysis, western blotting, and confocal microscopy. Taken together, these data suggest that the phage affects the innate response, such as the IFN-inducible GTPases and GBPs, and therefore exerts an antiviral effect in vitro. Collectively, our findings provide insights into the interactions of immune cells and phages, which establish phage-based antiviral effects.

噬菌体（噬菌体）是细菌的病毒。尽管关于噬菌体与真核细胞相互作用的研究不断取得进展，但我们对噬菌体的作用及其潜在影响的理解仍然不完整。本研究的目的是调查金黄色葡萄球菌的影响噬菌体 vB_SauM_JS25 对鼠诺如病毒 (MNV) 复制的影响。使用 RAW 264.7 细胞系进行实验。噬菌体处理后，MNV 增殖被显着抑制，如实时定量聚合酶链反应 (RT-qPCR) 分析、蛋白质印迹、50% 组织培养感染剂量和免疫荧光所示。此外，我们通过 RNA 测序 (RNA-seq) 和生物信息学分析揭示了噬菌体/MNV 共孵育的 RAW 264.7 细胞的转录变化。我们随后的分析表明，先天免疫反应可能在限制 MNV 复制中起重要作用，例如细胞对 IFN-γ 的反应和对 IFN-γ 的反应。此外，IL-10、Arg-1、Ccl22、GBP2、GBP3、GBP5和GBP7的基因表达显着增加，这表明 RT-qPCR 和 RNA-seq 结果之间存在很强的相关性。此外，如 RT-qPCR 分析、蛋白质印迹和共聚焦显微镜所揭示的，噬菌体处理激活了鸟苷酸结合蛋白 (GBP)。总之，这些数据表明噬菌体影响先天反应，例如 IFN 诱导的 GTP 酶和 GBP，因此在体外发挥抗病毒作用。总的来说，我们的研究结果提供了对免疫细胞和噬菌体相互作用的见解，从而建立了基于噬菌体的抗病毒作用。