Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China
J Virol. 2021 Feb 24;95(6). doi: 10.1128/JVI.02038-20.
Guanylate-binding protein 7 (GBP7) belongs to the GBP family, which plays key roles in mediating innate immune responses to intracellular pathogens. Thus far, GBP7 has been reported to be a critical cellular factor against bacterial infection. However, the relationship between GBP7 and influenza A virus (IAV) replication is unknown. Here, we showed that GBP7 expression was significantly upregulated in the lungs of mice, human peripheral blood mononuclear cells (PBMCs), and A549 cells during IAV infection. Using the CRISPR-Cas9 system and overexpression approaches, it was found that GBP7 knockout inhibited IAV replication by enhancing the expression of IAV-induced type I interferon (IFN), type III IFN, and proinflammatory cytokines. Conversely, overexpression of GBP7 facilitated IAV replication by suppressing the expression of those factors. Furthermore, GBP7 knockout enhanced IAV-induced nuclear factor-κB (NF-κB) activation and phosphorylation of stat1 and stat2; overexpression of GBP7 had the opposite effect. Our data indicated that GBP7 suppresses innate immune responses to IAV infection via NF-κB and JAK-STAT signaling pathways. Taken together, upon IAV infection, the induced GBP7 facilitated IAV replication by suppressing innate immune responses to IAV infection, which suggested that GBP7 serves as a therapeutic target for controlling IAV infection. So far, few studies have mentioned the distinct function of guanylate-binding protein 7 (GBP7) on virus infection. Here, we reported that GBP7 expression was significantly upregulated in the lungs of mice, human PBMCs, and A549 cells during IAV infection. GBP7 facilitated IAV replication by suppressing the expression of type I interferon (IFN), type III IFN, and proinflammatory cytokines. Furthermore, it was indicated that GBP7 suppresses innate immune responses to IAV infection via NF-κB and JAK-STAT signaling pathways. Taken together, our results elucidate a critical role of GBP7 in the host immune system during IAV infection.
鸟苷酸结合蛋白 7（GBP7）属于 GBP 家族，在介导细胞内病原体的固有免疫反应中发挥关键作用。到目前为止，已经报道 GBP7 是对抗细菌感染的关键细胞因子。然而，GBP7 与流感 A 病毒（IAV）复制之间的关系尚不清楚。在这里，我们发现在 IAV 感染期间，GBP7 在小鼠肺部、人外周血单核细胞（PBMCs）和 A549 细胞中的表达明显上调。使用 CRISPR-Cas9 系统和过表达方法，发现 GBP7 敲除通过增强 IAV 诱导的 I 型干扰素（IFN）、III 型 IFN 和促炎细胞因子的表达抑制 IAV 复制。相反，GBP7 的过表达通过抑制这些因子的表达促进 IAV 复制。此外，GBP7 敲除增强了 IAV 诱导的核因子-κB（NF-κB）激活和 stat1 和 stat2 的磷酸化；GBP7 的过表达则产生相反的效果。我们的数据表明，GBP7 通过 NF-κB 和 JAK-STAT 信号通路抑制对 IAV 感染的固有免疫反应。综上所述，在 IAV 感染后，诱导的 GBP7 通过抑制对 IAV 感染的固有免疫反应促进了 IAV 的复制，这表明 GBP7 可作为控制 IAV 感染的治疗靶点。到目前为止，很少有研究提到鸟苷酸结合蛋白 7（GBP7）在病毒感染方面的独特功能。在这里，我们报道在 IAV 感染期间，GBP7 在小鼠肺部、人 PBMCs 和 A549 细胞中的表达明显上调。GBP7 通过抑制 I 型干扰素（IFN）、III 型 IFN 和促炎细胞因子的表达促进了 IAV 的复制。此外，表明 GBP7 通过 NF-κB 和 JAK-STAT 信号通路抑制对 IAV 感染的固有免疫反应。综上所述，我们的结果阐明了 GBP7 在 IAV 感染期间宿主免疫系统中的关键作用。
