tetano
Editor, Senior Moderator
Virol J
. 2022 Nov 3;19(1):176.
doi: 10.1186/s12985-022-01907-x.
Tripartite motif-containing protein 46 accelerates influenza A H7N9 virus infection by promoting K48-linked ubiquitination of TBK1
Wei Su[SUP] #[/SUP][SUP] 1 [/SUP], Xian-Tian Lin[SUP] #[/SUP][SUP] 2 [/SUP], Shuai Zhao[SUP] #[/SUP][SUP] 2 [/SUP], Xiao-Qin Zheng[SUP] 3 [/SUP], Yu-Qing Zhou[SUP] 4 [/SUP], Lan-Lan Xiao[SUP] 2 [/SUP], Hui Chen[SUP] 2 [/SUP], Zheng-Yu Zhang[SUP] 2 [/SUP], Li-Jun Zhang[SUP] 2 [/SUP], Xiao-Xin Wu[SUP] 5 [/SUP]
Affiliations
Abstract
Background: Avian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive.
Methods: Herein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1).
Results: Type I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection.
Conclusion: Our results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.
Keywords: Influenza A H7N9; Interferons; TBK1; TRIM46.
. 2022 Nov 3;19(1):176.
doi: 10.1186/s12985-022-01907-x.
Tripartite motif-containing protein 46 accelerates influenza A H7N9 virus infection by promoting K48-linked ubiquitination of TBK1
Wei Su[SUP] #[/SUP][SUP] 1 [/SUP], Xian-Tian Lin[SUP] #[/SUP][SUP] 2 [/SUP], Shuai Zhao[SUP] #[/SUP][SUP] 2 [/SUP], Xiao-Qin Zheng[SUP] 3 [/SUP], Yu-Qing Zhou[SUP] 4 [/SUP], Lan-Lan Xiao[SUP] 2 [/SUP], Hui Chen[SUP] 2 [/SUP], Zheng-Yu Zhang[SUP] 2 [/SUP], Li-Jun Zhang[SUP] 2 [/SUP], Xiao-Xin Wu[SUP] 5 [/SUP]
Affiliations
- PMID: 36329446
- DOI: 10.1186/s12985-022-01907-x
Abstract
Background: Avian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive.
Methods: Herein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1).
Results: Type I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection.
Conclusion: Our results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.
Keywords: Influenza A H7N9; Interferons; TBK1; TRIM46.