tetano
Editor, Senior Moderator
BMC Infect Dis
. 2025 Jan 20;25(1):83.
doi: 10.1186/s12879-025-10490-9. Lung-specific CRBN knockout attenuates influenza a virus-induced acute lung injury in mice: a potential therapeutic approach
Lifang Zhang[SUP] 1 [/SUP], Qingchao Zhang[SUP] 1 [/SUP], Jiahui Chang[SUP] 1 [/SUP], Yunyi Zhou[SUP] 1 [/SUP], Wei Wang[SUP] 1 [/SUP], Xiliang Wang[SUP] 2 [/SUP], Chengyu Jiang[SUP] 3 [/SUP], Yanli Zhang[SUP] 4 [/SUP]
Affiliations
Influenza-related acute lung injury is a life-threatening condition primarily caused by uncontrolled replication of the influenza virus and intense proinflammatory responses. Cereblon (CRBN) is a protein known for its role in the ubiquitin-proteasome system and as a target of the drug thalidomide. However, the function of CRBN in influenza virus infection remains poorly understood. In this study, we investigated the impact of CRBN on A/Puerto Rico/8/34 (PR8) influenza virus-induced lung injury and its potential as a therapeutic target. Knocking down CRBN in vitro significantly reduces PR8-induced cell death. Using Sftpc-Cre; Crbn[SUP]flox/flox[/SUP] lung-specific Crbn knockout mice, we demonstrated that Crbn deficiency significantly decreased mortality, weight loss, lung pathology, edema, and viral load in PR8-infected mice. PR8-infected Sftpc-Cre; Crbn[SUP]flox/flox[/SUP] mice exhibited a marked reduction in lung inflammatory cell infiltration and suppression of MAPK pathway activation, highlighted by a significant downregulation of the MKK4-JNK-c-JUN signaling cascade. Collectively, these findings indicate that CRBN plays a pivotal role in the pathogenesis of influenza-induced lung injury by modulating MAPK pathway signaling, underscoring its therapeutic potential as a target for intervention.
Keywords: Acute lung injury; CRBN; H1N1; Influenza a virus.
. 2025 Jan 20;25(1):83.
doi: 10.1186/s12879-025-10490-9. Lung-specific CRBN knockout attenuates influenza a virus-induced acute lung injury in mice: a potential therapeutic approach
Lifang Zhang[SUP] 1 [/SUP], Qingchao Zhang[SUP] 1 [/SUP], Jiahui Chang[SUP] 1 [/SUP], Yunyi Zhou[SUP] 1 [/SUP], Wei Wang[SUP] 1 [/SUP], Xiliang Wang[SUP] 2 [/SUP], Chengyu Jiang[SUP] 3 [/SUP], Yanli Zhang[SUP] 4 [/SUP]
Affiliations
- PMID: 39833740
- DOI: 10.1186/s12879-025-10490-9
Influenza-related acute lung injury is a life-threatening condition primarily caused by uncontrolled replication of the influenza virus and intense proinflammatory responses. Cereblon (CRBN) is a protein known for its role in the ubiquitin-proteasome system and as a target of the drug thalidomide. However, the function of CRBN in influenza virus infection remains poorly understood. In this study, we investigated the impact of CRBN on A/Puerto Rico/8/34 (PR8) influenza virus-induced lung injury and its potential as a therapeutic target. Knocking down CRBN in vitro significantly reduces PR8-induced cell death. Using Sftpc-Cre; Crbn[SUP]flox/flox[/SUP] lung-specific Crbn knockout mice, we demonstrated that Crbn deficiency significantly decreased mortality, weight loss, lung pathology, edema, and viral load in PR8-infected mice. PR8-infected Sftpc-Cre; Crbn[SUP]flox/flox[/SUP] mice exhibited a marked reduction in lung inflammatory cell infiltration and suppression of MAPK pathway activation, highlighted by a significant downregulation of the MKK4-JNK-c-JUN signaling cascade. Collectively, these findings indicate that CRBN plays a pivotal role in the pathogenesis of influenza-induced lung injury by modulating MAPK pathway signaling, underscoring its therapeutic potential as a target for intervention.
Keywords: Acute lung injury; CRBN; H1N1; Influenza a virus.