Evidence map›Paper›PMID 28076420›Full record

ArticlePLoS pathogens2017

Chaperone-Mediated Autophagy Protein BAG3 Negatively Regulates Ebola and Marburg VP40-Mediated Egress.

Jingjing Liang, Cari A Sagum, Mark T Bedford, Sachdev S Sidhu, Marius Sudol, Ziying Han, Ronald N Harty

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

40 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. The Pathology of Viral Infections.Advances in experimental medicine and biology · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Research progress on the mechanism of exosome-mediated virus infection.Frontiers in cellular and infection microbiology · 2024
    Review
  10. Article
  11. Article
  12. Chaperone-assisted selective autophagy targets filovirus VP40 as a client and restricts egress of virus particles.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Compound FC-10696 Inhibits Egress of Marburg Virus.Antimicrobial agents and chemotherapy · 2021
    Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 5 countries.

Jingjing LiangDepartment of Pathobiology, School Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Cari A SagumDepartment of Epigenetics & Molecular Carcinogenesis, M.D. Anderson Cancer Center, University of Texas Smithville, Smithville, TX, United States of America.
Mark T BedfordDepartment of Epigenetics & Molecular Carcinogenesis, M.D. Anderson Cancer Center, University of Texas Smithville, Smithville, TX, United States of America.
Sachdev S SidhuDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada.ORCID 0000-0001-7755-5918
Marius SudolDepartment of Physiology, National University of Singapore, Mechanobiology Institute and Institute for Molecular and Cell Biology (IMCB, A*STAR), Republic of Singapore.
Ziying HanDepartment of Pathobiology, School Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Ronald N HartyDepartment of Pathobiology, School Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.ORCID 0000-0001-6596-0414
The University of Texas MD Anderson Cancer Center · USUniversity of Pennsylvania · USAgency for Science, Technology and Research · SGGuangxi University · CNUniversity of Toronto · CA

Funding

Host-Oriented Therapeutics Targeting Filovirus Budding.R33AI102104 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HARTY, RONALD N · 2014 to 2016
$1.4M
Innate Immune Regulation of Intracellular Pathways Involved in Filovirus BuddingR21AI103785 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HARTY, RONALD N · 2014 to 2015
$440k
Host-Oriented Therapeutics Targeting Filovirus Budding.R21AI102104 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HARTY, RONALD N · 2012 to 2013
$423k
DEVELOPMENT OF SMALL MOLECULE THERAPEUTICS AGAINST RNA VIRUSESR41AI113952 · NIAID · FOX CHASE CHEMICAL DIVERSITY CENTER, INC · PI HARTY, RONALD N · 2015 to 2015
$300k
NIAID NIH HHS R21 AI102104NIAID NIH HHS R21 AI103785NIAID NIH HHS R33 AI102104NIAID NIH HHS R41 AI113952
6 · The paper itself

Abstract

Ebola (EBOV) and Marburg (MARV) viruses are members of the Filoviridae family which cause outbreaks of hemorrhagic fever. The filovirus VP40 matrix protein is essential for virus assembly and budding, and its PPxY L-domain motif interacts with WW-domains of specific host proteins, such as Nedd4 and ITCH, to facilitate the late stage of virus-cell separation. To identify additional WW-domain-bearing host proteins that interact with VP40, we used an EBOV PPxY-containing peptide to screen an array of 115 mammalian WW-domain-bearing proteins. Using this unbiased approach, we identified BCL2 Associated Athanogene 3 (BAG3), a member of the BAG family of molecular chaperone proteins, as a specific VP40 PPxY interactor. Here, we demonstrate that the WW-domain of BAG3 interacts with the PPxY motif of both EBOV and MARV VP40 and, unexpectedly, inhibits budding of both eVP40 and mVP40 virus-like particles (VLPs), as well as infectious VSV-EBOV recombinants. BAG3 is a stress induced protein that regulates cellular protein homeostasis and cell survival through chaperone-mediated autophagy (CMA). Interestingly, our results show that BAG3 alters the intracellular localization of VP40 by sequestering VP40 away from the plasma membrane. As BAG3 is the first WW-domain interactor identified that negatively regulates budding of VP40 VLPs and infectious virus, we propose that the chaperone-mediated autophagy function of BAG3 represents a specific host defense strategy to counteract the function of VP40 in promoting efficient egress and spread of virus particles.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsApoptosis Regulatory ProteinsAutophagyCell Line, TumorCell SurvivalCricetinaeEbolavirusEndosomal Sorting Complexes Required for TransportHEK293 CellsHeLa CellsHemorrhagic Fever, EbolaHumansMarburgvirusMarburg Virus DiseaseNedd4 Ubiquitin Protein LigasesAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsBAG3 protein, humanEndosomal Sorting Complexes Required for TransportITCH protein, humanNedd4 protein, humanNedd4 Ubiquitin Protein LigasesPPXY ligandProlineRepressor ProteinsRNA, Small InterferingUbiquitin-Protein LigasesViral Matrix ProteinsVP40 protein, virus

Identifiers

PMID28076420
PMCPMC5226679
OpenAlexW2573232933

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.