Ivns1abp-KO Mouse

Ivns1abp, also known as Influenza Virus NS1A Binding Protein, belongs to the Kelch family of proteins. It plays a central role in actin cytoskeleton dynamics by directly associating with F-actin and protecting against actin derangement. It may be a critical regulator of the macrophage phenotype and function under inflammatory conditions. It also participates in the splicing and nuclear export of influenza virus M mRNAs, interacting with components of the splicing and mRNA export machineries [4,5,6].

In a study on primary immunodeficiency (PID), a Bayesian approach identified IVNS1ABP as a new candidate PID-associated gene through whole-genome sequencing in a large PID cohort. In liver cancer, epigenetic inactivation of NSUN7 leads to a decrease in the protein levels of its partner IVNS1ABP, creating sensitivity to bromodomain inhibitors. In acute myocardial infarction, IVNS1ABP is part of a neutrophil-derived PCD signature that can predict and stratify patients [1,2,3].

In conclusion, Ivns1abp is crucial for cytoskeleton preservation and macrophage function in inflammation, and is also involved in viral mRNA processing. Its role in diseases such as primary immunodeficiency, liver cancer, and acute myocardial infarction, as revealed through these studies, highlights its significance in understanding disease mechanisms and potential therapeutic targets.

References:

1. Thaventhiran, James E D, Lango Allen, Hana, Burren, Oliver S, Thrasher, Adrian J, Smith, Kenneth G C. 2020. Whole-genome sequencing of a sporadic primary immunodeficiency cohort. In Nature, 583, 90-95. doi:10.1038/s41586-020-2265-1. https://pubmed.ncbi.nlm.nih.gov/32499645/

2. Ortiz-Barahona, Vanessa, Soler, Marta, Davalos, Veronica, Llovet, Josep M, Esteller, Manel. 2023. Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer. In Molecular cancer, 22, 83. doi:10.1186/s12943-023-01785-z. https://pubmed.ncbi.nlm.nih.gov/37173708/

3. Zhu, Yihao, Chen, Yuxi, Zu, Yao. 2024. Leveraging a neutrophil-derived PCD signature to predict and stratify patients with acute myocardial infarction: from AI prediction to biological interpretation. In Journal of translational medicine, 22, 612. doi:10.1186/s12967-024-05415-0. https://pubmed.ncbi.nlm.nih.gov/38956669/

4. Hotter, Georgina, Mastora, Chrysoula, Jung, Michaela, Guiteras, Roser, Sola, Anna. 2020. The influenza virus NS1A binding protein gene modulates macrophages response to cytokines and phagocytic potential in inflammation. In Scientific reports, 10, 15302. doi:10.1038/s41598-020-72342-7. https://pubmed.ncbi.nlm.nih.gov/32943673/

5. Zhang, Ke, Cagatay, Tolga, Xie, Dongqi, Ren, Yi, Fontoura, Beatriz M A. 2024. Cellular NS1-BP protein interacts with the mRNA export receptor NXF1 to mediate nuclear export of influenza virus M mRNAs. In The Journal of biological chemistry, 300, 107871. doi:10.1016/j.jbc.2024.107871. https://pubmed.ncbi.nlm.nih.gov/39384042/

6. Zhang, Ke, Shang, Guijun, Padavannil, Abhilash, Chook, Yuh Min, Fontoura, Beatriz M A. 2018. Structural-functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression. In Proceedings of the National Academy of Sciences of the United States of America, 115, E12218-E12227. doi:10.1073/pnas.1818012115. https://pubmed.ncbi.nlm.nih.gov/30538201/