Evidence map›Paper›PMID 35263388›Full record

ArticlePLoS pathogens2022

Reovirus infection is regulated by NPC1 and endosomal cholesterol homeostasis.

Paula Ortega-Gonzalez, Gwen Taylor, Rohit K Jangra, Raquel Tenorio, Isabel Fernandez de Castro, Bernardo A Mainou, Robert C Orchard, Craig B Wilen, Pamela H Brigleb, Jorna Sojati and 4 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 2 countries.

Paula Ortega-GonzalezCell Structure Laboratory, National Center for Biotechnology, CNB-CSIC, campus UAM, Cantoblanco, Madrid, Spain.ORCID 0000-0003-2882-3271
Gwen TaylorDepartment of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0002-9276-087X
Rohit K JangraDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.ORCID 0000-0002-3119-0869
Raquel TenorioCell Structure Laboratory, National Center for Biotechnology, CNB-CSIC, campus UAM, Cantoblanco, Madrid, Spain.ORCID 0000-0003-0547-155X
Isabel Fernandez de CastroCell Structure Laboratory, National Center for Biotechnology, CNB-CSIC, campus UAM, Cantoblanco, Madrid, Spain.ORCID 0000-0002-5388-8934
Bernardo A MainouDepartment of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.ORCID 0000-0002-7721-183X
Robert C OrchardDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.ORCID 0000-0001-8216-4946
Craig B WilenDepartments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Pamela H BriglebInstitute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Jorna SojatiInstitute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0002-3908-6126
Kartik ChandranDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Martin SachseCell Structure Laboratory, National Center for Biotechnology, CNB-CSIC, campus UAM, Cantoblanco, Madrid, Spain.
Cristina RiscoCell Structure Laboratory, National Center for Biotechnology, CNB-CSIC, campus UAM, Cantoblanco, Madrid, Spain.ORCID 0000-0001-7501-5934
Terence S DermodyDepartment of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0003-1853-8741
University of Pittsburgh · USCentro Nacional de Biotecnología · ESAlbert Einstein College of Medicine · USThe University of Texas Southwestern Medical Center · USVanderbilt University · USYale University · US

Funding

TRAINING PROGRAM FOR MD/PHD STUDENTST32GM008208 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STEINMAN, RICHARD A · 1987 to 2021
$15.4M
CELL ENTRY OF REOVIRUSR01AI032539 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI TERENCE S. DERMODY · 1998 to 2026
$12.3M
Immunology of Infectious DiseaseT32AI060525 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JoAnne L. Flynn · 2005 to 2026
$5.3M
Overcoming host Genetic Redundancy and Pathogen Subversion to Define new host-viral InterfacesR35GM142684 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI ORCHARD, ROBERT C. · 2021 to 2025
$2.0M
Host-virus interactions in the control of filovirus entryR01AI134824 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CHANDRAN, KARTIK · 2018 to 2021
$1.9M
NIAID NIH HHS R01 AI032539NIAID NIH HHS R01 AI134824NIAID NIH HHS T32 AI060525NIGMS NIH HHS R35 GM142684NIGMS NIH HHS T32 GM008208
6 · The paper itself

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.

Indexed as

ReoviridaeReoviridae InfectionsAnimalsCholesterolEndosomesHomeostasisHumansMammalsNiemann-Pick C1 ProteinCholesterolNiemann-Pick C1 ProteinNPC1 protein, human

Identifiers

PMID35263388
PMCPMC8906592
OpenAlexW4220729641

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Registered trials

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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.