Feng M, Zhang Q, Wu W, Chen L, Gu S, Ye Y, Zhong Y. Inducible Guanylate-Binding Protein 7 Facilitates Influenza A Virus Replication by Suppressing Innate Immunity via NF-κB and JAK-STAT Signaling Pathways. J Virol. 2021 Jan 6: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 up-regulated 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 might serve as a potential therapeutic target for controlling IAV infection.IMPORTANCE 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 up-regulated 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 host immune system during IAV infection.
See Also:
Latest articles in those days:
- Evolution of H7N9 highly pathogenic avian influenza virus in the context of vaccination 20 hours ago
- Cost-effectiveness of high-dose influenza vaccination in the Netherlands: Incorporating the impact on both respiratory and cardiovascular hospitalizations 20 hours ago
- First human case of avian influenza A (H10N3) in Southwest China [preprint] 3 days ago
- Molecular characterization of the whole genome of H9N2 avian influenza virus isolated from Egyptian poultry farms 3 days ago
- Genetic drift and purifying selection shape within-host influenza A virus populations during natural swine infections 3 days ago
[Go Top] [Close Window]