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Antiviral effect of a bacteriophage on murine norovirus replication via modulation of the innate immune response

文献类型： 外文期刊

作者： Zhang, Lili 1 ; Ma, Chang 2 ; Liu, Jie 2 ; Shahin, Khashayar 1 ; Hou, Xiang 1 ; Sun, Lichang 1 ; Wang, Heye 1 ; Wang, Ran 1 ;

作者机构： 1.Jiangsu Acad Agr Sci, Inst Food Safety & Nutr, Jiangsu Prov State Key Lab Breeding Base, Key Lab Food Qual & Safety, Nanjing 210014, Peoples R China

2.Jinling Hosp, Dept Comparat Med, 305 East Zhongshan Rd, Nanjing 210002, Peoples R China

3.Jiangsu Univ, Zhenjiang, Jiangsu, Peoples R China

4.Chinese Acad Sci, Inst Pasteur Shanghai, Ctr Microbes Dev & Hlth CMDH, Expt Bacteriol Lab, Beijing, Peoples R China

关键词： Bacteriophages; Norovirus; Macrophages; Antiviral agents; Interferons

期刊名称：VIRUS RESEARCH （ 影响因子：3.303； 五年影响因子：3.445 ）

ISSN： 0168-1702

年卷期： 2021 年 305 卷

页码：

收录情况： SCI

摘要： 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-gamma and response to IFN-gamma. 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.

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