title: Inducible GBP5 Mediates the Antiviral Response via Interferon-Related Pathways during Influenza A Virus Infection.
abstract: Guanylate binding protein (GBP) 5 belongs to the GBP family, which is involved in important cellular processes, including signal transduction, translation, vesicle trafficking, and exocytosis. Structurally, GBPs display a high degree of homology and share highly conserved GTP-binding or hydrolysis domains. GBP5 was reported to be a critical cellular factor in inflammasome assembly. However, little is known about its role in the host antiviral innate immune response. In this study, we found that GBP5 expression was significantly elevated in influenza patients and influenza A virus-infected A549 human lung epithelial cells. The overexpression of GBP5 inhibited virus replication by enhancing the expression of virus-induced interferon (IFN) and IFN-related effectors. Knockdown of GBP5 had the opposite effect. Moreover, GBP5 enhanced endogenous IFN expression by interacting with the NF-κB-essential modulator complex and stimulating NF-κB signaling. Additionally, the expression of proinflammatory factors, such as IL-6, IL-8, tumor necrosis factor-α, cyclooxygenase-2, and inducible nitric oxide synthase, was also activated by GBP5. Taken together, our results reveal that GBP5 inhibited virus replication through the activation of IFN signaling and proinflammatory factors.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Feng
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Cao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yushun
authors.initials: Y
authors.lastname: Wan
authors.forename: Nanfang
authors.initials: N
authors.lastname: Peng
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000072283:A549 Cells; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D009980:Influenza A virus / Q000502:physiology*; D007251:Influenza, Human / Q000276:immunology*; D007372:Interferons / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020545:Respiratory Mucosa / Q000276:immunology* / Q000821:virology; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: D016207:Cytokines; C528873:GBP5 protein, human; D058847:Inflammasomes; D018836:Inflammation Mediators; D016328:NF-kappa B; D034741:RNA, Small Interfering; D007372:Interferons; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D019204:GTP-Binding Proteins
keywords: Cyclooxygenase-2; Guanylate binding protein 5; Influenza A virus; Interferon signaling; NF-κB-essential modulator