Phospholipid Scramblase 1 (PLSCR1) Regulates Interferon-Lambda Receptor 1 (IFN-λR1) and IFN-λ Signaling in Influenza A Virus (IAV) Infection

• DOI: 10.7554/elife.104359
• Publication Date: 2025-03-11T13:25:31Z
• Authors: Alina X Yang; Lisa Ramos-Rodriguez; Parand Sorkhdini; Dongqin Yang; Carmelissa Norbrun; Sonoor Majid; Yong Zhang; Michael J Holtzman; David F Boyd; Yang Zhou
• Keywords: Phospholipid scramblase

Phospholipid scramblase 1 (PLSCR1) is an antiviral interferon-stimulated gene (ISG) that has several known anti-influenza functions such as interfering with viral nuclear import, regulating toll-like receptor (TLR) 9 and potentiating the expression of other ISGs. However, exact mechanisms anti-flu activity PLSCR1 in relation to its compartment enzymatic activity, molecular cellular involved have not been completely explored. Moreover, only limited animal models studied delineate role at tissue level influenza infections. We hypothesize protects hosts against IAV infection by type 3 interferon (IFN-λ) signaling pathways. Our results showed Plscr1 was highly induced vivo epithelial cells treated IFN-λ. found knockout (KO) mice exhibited exacerbated body weight loss, decreased survival rates, heightened replication, increased lung damage. Interestingly, transcriptomic analyses demonstrated required for (Ifn-λr1) expression, impaired Ifn-λr1 downstream ISGs may be responsible delayed clearance KO mice. In addition, interacted within following infection, suggesting modulate IFN-λ via protein-protein interactions. Finally, single-cell RNA sequencing data indicated significantly upregulated ciliated airway infection. Consistently, floxStop Foxj1-Cre + cell-specific overexpression reduced susceptibility, less inflammation enhanced research will elucidate virus-host interactions pave way development novel drugs target human elements like PLSCR1, thereby mitigating emergence drug-resistant strains.