Gbp7-KO Mouse

Gbp7, a member of the guanylate-binding protein (GBP) family, is an interferon-inducible guanosine triphosphatase (GTPase). GBPs play key roles in host defense against intracellular pathogens, and Gbp7 is involved in innate immune responses [1,2,3,4]. It is also associated with various signaling pathways, such as NF-κB and JAK-STAT [2].

In influenza A virus (IAV) infection, Gbp7 knockout in mice enhanced IAV-induced nuclear factor-κB (NF-κB) activation and phosphorylation of stat1 and stat2, inhibiting IAV replication by increasing the expression of type I interferon (IFN), type III IFN, and proinflammatory cytokines. Conversely, overexpression of Gbp7 facilitated IAV replication by suppressing these factors, indicating Gbp7 suppresses innate immune responses to IAV via NF-κB and JAK-STAT signaling pathways [2]. In bacterial infections, at least four Gbps including Gbp7 conferred cell-autonomous immunity to listerial or mycobacterial infection within macrophages and gene-deficient animals. These Gbps recruited host defense proteins to kill intracellular bacteria [4].

In conclusion, Gbp7 has important functions in the innate immune response, especially in the body's defense against viral and bacterial infections. Gene knockout mouse models have been crucial in revealing that Gbp7 can either promote or inhibit pathogen replication by modulating the innate immune response, which provides potential therapeutic targets for controlling relevant infections.

References:

1. Legewie, Larissa, Loschwitz, Jennifer, Steffens, Nora, Degrandi, Daniel, Pfeffer, Klaus. . Biochemical and structural characterization of murine GBP7, a guanylate binding protein with an elongated C-terminal tail. In The Biochemical journal, 476, 3161-3182. doi:10.1042/BCJ20190364. https://pubmed.ncbi.nlm.nih.gov/31689351/

2. Feng, Mingkai, Zhang, Qiao, Wu, Wenjiao, Huang, Qi, Liu, Shuwen. 2021. Inducible Guanylate-Binding Protein 7 Facilitates Influenza A Virus Replication by Suppressing Innate Immunity via NF-κB and JAK-STAT Signaling Pathways. In Journal of virology, 95, . doi:10.1128/JVI.02038-20. https://pubmed.ncbi.nlm.nih.gov/33408175/

3. Marinho, Fabio V, Brito, Camila, de Araujo, Ana Carolina V S C, Oliveira, Sergio C. 2024. Guanylate-binding protein-5 is involved in inflammasome activation by bacterial DNA but only the cooperation of multiple GBPs accounts for control of Brucella abortus infection. In Frontiers in immunology, 15, 1341464. doi:10.3389/fimmu.2024.1341464. https://pubmed.ncbi.nlm.nih.gov/38404575/

4. Kim, Bae-Hoon, Shenoy, Avinash R, Kumar, Pradeep, Tiwari, Sangeeta, MacMicking, John D. . A family of IFN-γ-inducible 65-kD GTPases protects against bacterial infection. In Science (New York, N.Y.), 332, 717-21. doi:10.1126/science.1201711. https://pubmed.ncbi.nlm.nih.gov/21551061/