ArticlePLoS pathogens2022
Reovirus infection is regulated by NPC1 and endosomal cholesterol homeostasis.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Review
- NPC1 promotes HTNV replication by controlling innate immune response.Frontiers in immunology · 2026Article
- Dynamic regulatory mechanism of cholesterol 25-hydroxylase-mediated antiviral response in RNA virus infections.Frontiers in cellular and infection microbiology · 2026Review
- Annexin A2 stabilizes the endoplasmic reticulum and actin cytoskeleton and influences the formation of reovirus factories.Journal of virology · 2025Article
- Ataxin-2-like promotes translation of nonpolyadenylated reovirus mRNA.Nature communications · 2025Article
- The role of lipids and lipids lowering drugs in human papillomavirus (HPV) and HPV-associated cancers.Infectious agents and cancer · 2025Review
- Cholesterol-Dependent Membrane Deformation by Metastable Viral Capsids Facilitates Entry.ACS infectious diseases · 2024Article
- NRP1 is a receptor for mammalian orthoreovirus engaged by distinct capsid subunits.Cell host & microbe · 2024Article
- Viral regulation of organelle membrane contact sites.PLoS biology · 2024Article
- Cholesterol-Dependent Membrane Deformation by Metastable Viral Capsids Facilitates Entry.bioRxiv : the preprint server for biology · 2024Article
- An overview of the role of Niemann-pick C1 (NPC1) in viral infections and inhibition of viral infections through NPC1 inhibitor.Cell communication and signaling : CCS · 2023Review
- Characterization of Sialic Acid-Independent Simian Rotavirus Mutants in Viral Infection and Pathogenesis.Journal of virology · 2023Article
- Host cellular factors involved in pseudorabies virus attachment and entry: a mini review.Frontiers in veterinary science · 2023Review
- Cholesterol 25-hydroxylase suppresses avian reovirus replication by its enzymatic product 25-hydroxycholesterol.Frontiers in microbiology · 2023Article
- A CRISPR-Cas9 screen reveals a role for WD repeat-containing protein 81 (WDR81) in the entry of late penetrating viruses.PLoS pathogens · 2022Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Cholesterol homeostasis is required for the replication of many viruses, including Ebola virus, hepatitis C virus, and human immunodeficiency virus-1. Niemann-Pick C1 (NPC1) is an endosomal-lysosomal membrane protein involved in cholesterol trafficking from late endosomes and lysosomes to the endoplasmic reticulum. We identified NPC1 in CRISPR and RNA interference screens as a putative host factor for infection by mammalian orthoreovirus (reovirus). Following internalization via clathrin-mediated endocytosis, the reovirus outer capsid is proteolytically removed, the endosomal membrane is disrupted, and the viral core is released into the cytoplasm where viral transcription, genome replication, and assembly take place. We found that reovirus infection is significantly impaired in cells lacking NPC1, but infection is restored by treatment of cells with hydroxypropyl-β-cyclodextrin, which binds and solubilizes cholesterol. Absence of NPC1 did not dampen infection by infectious subvirion particles, which are reovirus disassembly intermediates that bypass the endocytic pathway for infection of target cells. NPC1 is not required for reovirus attachment to the plasma membrane, internalization into cells, or uncoating within endosomes. Instead, NPC1 is required for delivery of transcriptionally active reovirus core particles from endosomes into the cytoplasm. These findings suggest that cholesterol homeostasis, ensured by NPC1 transport activity, is required for reovirus penetration into the cytoplasm, pointing to a new function for NPC1 and cholesterol homeostasis in viral infection.
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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.