Phospholipid scramblase 1: a frontline defense against viral infections

Phospholipid scramblase 1 (PLSCR1) is the most studied member of the phospholipid scramblase protein family. Its main function is to catalyze calcium (Ca2+)-dependent, ATP-independent, bidirectional and non-specific translocation of phospholipids between inner and outer leaflets of plasma membrane....

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Main Authors: Alina X. Yang, Carmelissa Norbrun, Parand Sorkhdini, Yang Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1573373/full
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author Alina X. Yang
Carmelissa Norbrun
Parand Sorkhdini
Yang Zhou
author_facet Alina X. Yang
Carmelissa Norbrun
Parand Sorkhdini
Yang Zhou
author_sort Alina X. Yang
collection DOAJ
description Phospholipid scramblase 1 (PLSCR1) is the most studied member of the phospholipid scramblase protein family. Its main function is to catalyze calcium (Ca2+)-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.
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spelling doaj-art-950b070f4e5740ffa64939e021d91cef2025-08-20T03:06:42ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-04-011510.3389/fcimb.2025.15733731573373Phospholipid scramblase 1: a frontline defense against viral infectionsAlina X. YangCarmelissa NorbrunParand SorkhdiniYang ZhouPhospholipid scramblase 1 (PLSCR1) is the most studied member of the phospholipid scramblase protein family. Its main function is to catalyze calcium (Ca2+)-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.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1573373/fullPLSCR1antiviralSARS-CoV-2influenza A virusHIVEpstein-Barr virus
spellingShingle Alina X. Yang
Carmelissa Norbrun
Parand Sorkhdini
Yang Zhou
Phospholipid scramblase 1: a frontline defense against viral infections
Frontiers in Cellular and Infection Microbiology
PLSCR1
antiviral
SARS-CoV-2
influenza A virus
HIV
Epstein-Barr virus
title Phospholipid scramblase 1: a frontline defense against viral infections
title_full Phospholipid scramblase 1: a frontline defense against viral infections
title_fullStr Phospholipid scramblase 1: a frontline defense against viral infections
title_full_unstemmed Phospholipid scramblase 1: a frontline defense against viral infections
title_short Phospholipid scramblase 1: a frontline defense against viral infections
title_sort phospholipid scramblase 1 a frontline defense against viral infections
topic PLSCR1
antiviral
SARS-CoV-2
influenza A virus
HIV
Epstein-Barr virus
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1573373/full
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AT carmelissanorbrun phospholipidscramblase1afrontlinedefenseagainstviralinfections
AT parandsorkhdini phospholipidscramblase1afrontlinedefenseagainstviralinfections
AT yangzhou phospholipidscramblase1afrontlinedefenseagainstviralinfections