Yang Alina X, Norbrun Carmelissa, Sorkhdini Parand, Zhou Yang
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, United States.
Front Cell Infect Microbiol. 2025 Apr 3;15:1573373. doi: 10.3389/fcimb.2025.1573373. eCollection 2025.
Phospholipid scramblase 1 (PLSCR1) is the most studied member of the phospholipid scramblase protein family. Its main function is to catalyze calcium (Ca)-dependent, ATP-independent, bidirectional and non-specific translocation of phospholipids between inner and outer leaflets of plasma membrane. Additionally, PLSCR1 is identified as an interferon-stimulated gene (ISG) with antiviral activities, and its expression can be highly induced by all types of interferons in various viral infections. Indeed, numerous studies have reported the direct antiviral activities of PLSCR1 through interrupting the replication processes of a variety of viruses, including entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), nuclear localization of influenza A virus (IAV), and transactivation of human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), human T-cell leukemia virus type-1 (HTLV1), human cytomegalovirus (HCMV) and hepatitis B virus (HBV). In addition to these direct antiviral activities, PLSCR1 also regulates endogenous immune components to defend against viruses in both nonimmune and immune cells. Such activities include potentiation of ISG transcription, activation of JAK/STAT pathway, upregulation of type 3 interferon receptor (IFN-λR1) and recruitment of Toll-like receptor 9 (TLR9). This review aims to summarize the current understanding of PLSCR1's multiple roles as a frontline defense against viral infections.
磷脂翻转酶1（PLSCR1）是磷脂翻转酶蛋白家族中研究最多的成员。其主要功能是催化细胞膜内外小叶之间钙离子（Ca）依赖性、ATP非依赖性、双向且非特异性的磷脂转运。此外，PLSCR1被鉴定为具有抗病毒活性的干扰素刺激基因（ISG），在各种病毒感染中，其表达可被所有类型的干扰素高度诱导。事实上，大量研究报道了PLSCR1通过中断多种病毒的复制过程而具有直接抗病毒活性，包括严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的进入、甲型流感病毒（IAV）的核定位以及人类免疫缺陷病毒（HIV）、爱泼斯坦-巴尔病毒（EBV）、人类T细胞白血病病毒1型（HTLV1）、人类巨细胞病毒（HCMV）和乙型肝炎病毒（HBV）的反式激活。除了这些直接抗病毒活性外，PLSCR1还调节内源性免疫成分，以在非免疫细胞和免疫细胞中抵御病毒。这些活性包括增强ISG转录、激活JAK/STAT途径、上调3型干扰素受体（IFN-λR1）以及招募Toll样受体9（TLR9）。本综述旨在总结目前对PLSCR1作为抗病毒感染一线防御的多种作用的理解。
