ArticlePLoS pathogens2018
Herpes simplex viruses activate phospholipid scramblase to redistribute phosphatidylserines and Akt to the outer leaflet of the plasma membrane and promote viral entry.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- A cell-impermeable kinase inhibitor uncovers outside-in signaling pathways that promote HIV-1 infection.Journal of virology · 2026Article
- Glypican-1 upregulation elicited in response to a cell-impermeable kinase inhibitor and its overexpression enhance HIV-1 infection.bioRxiv : the preprint server for biology · 2025Article
- PLSCR1 suppresses SARS-CoV-2 infection by downregulating cell surface ACE2.Journal of virology · 2025Article
- Phospholipid scramblase 1: a frontline defense against viral infections.Frontiers in cellular and infection microbiology · 2025Review
- Phospholipid scramblase 1: an essential component of the nephrocyte slit diaphragm.Cellular and molecular life sciences : CMLS · 2024Article
- Modifications of the PI3K/Akt/mTOR axis during FeHV-1 infection in permissive cells.Frontiers in veterinary science · 2023Article
- Cell-impermeable staurosporine analog targets extracellular kinases to inhibit HSV and SARS-CoV-2.Communications biology · 2022Article
- Live and let die: signaling AKTivation and UPRegulation dynamics in SARS-CoVs infection and cancer.Cell death & disease · 2022Review
- Phospholipid scramblase 1: a protein with multiple functions via multiple molecular interactors.Cell communication and signaling : CCS · 2022Review
- Scrambled or flipped: 5 facts about how cellular phosphatidylserine localization can mediate viral replication.PLoS pathogens · 2022Article
- The Interferon-Inducible Human PLSCR1 Protein Is a Restriction Factor of Human Cytomegalovirus.Microbiology spectrum · 2022Article
- Exposure of a specific pleioform of multifunctional glyceraldehyde 3-phosphate dehydrogenase initiates CD14-dependent clearance of apoptotic cells.Cell death & disease · 2021Article
- Transcriptional profiling reveals potential involvement of microvillous TRPM5-expressing cells in viral infection of the olfactory epithelium.BMC genomics · 2021Article
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- Various Facets of Pathogenic Lipids in Infectious Diseases: Exploring Virulent Lipid-Host Interactome and Their Druggability.The Journal of membrane biology · 2020Review
- Lipidomics Issues on Human Positive ssRNA Virus Infection: An Update.Metabolites · 2020Review
- Differentially-Charged Liposomes Interact with Alphaherpesviruses and Interfere with Virus Entry.Pathogens (Basel, Switzerland) · 2020Article
- The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus.Frontiers in neurology · 2020Article
- Protein- and Peptide-Based Virus Inactivators: Inactivating Viruses Before Their Entry Into Cells.Frontiers in microbiology · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Herpes simplex virus (HSV) entry is associated with Akt translocation to the outer leaflet of the plasma membrane to promote a complex signaling cascade. We hypothesized that phospholipid scramblase-1 (PLSCR1), a calcium responsive enzyme that flips phosphatidylserines between membrane leaflets, might redistribute Akt to the outside during entry. Confocal imaging, biotinylation of membrane proteins and flow cytometric analysis demonstrated that HSV activates PLSCR1 and flips phosphatidylserines and Akt to the outside shortly following HSV-1 or HSV-2 exposure. Translocation was blocked by addition of a cell permeable calcium chelator, pharmacological scramblase antagonist, or transfection with small interfering RNA targeting PLSCR1. Co-immunoprecipitation and proximity ligation studies demonstrated that PLSCR1 associated with glycoprotein L at the outer leaflet and studies with gL deletion viruses indicate that this interaction facilitates subsequent restoration of the plasma membrane architecture. Ionomycin, a calcium ionophore, also induced PLSCR1 activation resulting in Akt externalization, suggesting a previously unrecognized biological phenomenon.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.