Evidence map›Paper›PMID 26317613›Full record

ArticlePLoS pathogens2015

Serine Phosphorylation of HIV-1 Vpu and Its Binding to Tetherin Regulates Interaction with Clathrin Adaptors.

Tonya Kueck, Toshana L Foster, Julia Weinelt, Jonathan C Sumner, Suzanne Pickering, Stuart J D Neil

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 5% 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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016
    Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Metformin Enhances Antibody-Mediated Recognition of HIV-Infected CD4bioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. Article
  10. Review
  11. ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
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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

6 authors at 2 institutions in 1 country.

Tonya KueckDepartment of Infectious Disease, King's College London School of Life Sciences and Medicine, Guy's Hospital, London, United Kingdom.
Toshana L FosterDepartment of Infectious Disease, King's College London School of Life Sciences and Medicine, Guy's Hospital, London, United Kingdom.
Julia WeineltDepartment of Infectious Disease, King's College London School of Life Sciences and Medicine, Guy's Hospital, London, United Kingdom.
Jonathan C SumnerDepartment of Infectious Disease, King's College London School of Life Sciences and Medicine, Guy's Hospital, London, United Kingdom.
Suzanne PickeringDepartment of Infectious Disease, King's College London School of Life Sciences and Medicine, Guy's Hospital, London, United Kingdom.
Stuart J D NeilDepartment of Infectious Disease, King's College London School of Life Sciences and Medicine, Guy's Hospital, London, United Kingdom.
King's College London · GBGuy's Hospital · GB

Funding

Medical Research Council G0801937Wellcome Trust 098049Wellcome Trust WT098049AIA
6 · The paper itself

Abstract

HIV-1 Vpu prevents incorporation of tetherin (BST2/ CD317) into budding virions and targets it for ESCRT-dependent endosomal degradation via a clathrin-dependent process. This requires a variant acidic dileucine-sorting motif (ExxxLV) in Vpu. Structural studies demonstrate that recombinant Vpu/tetherin fusions can form a ternary complex with the clathrin adaptor AP-1. However, open questions still exist about Vpu's mechanism of action. Particularly, whether endosomal degradation and the recruitment of the E3 ubiquitin ligase SCFβTRCP1/2 to a conserved phosphorylated binding site, DSGNES, are required for antagonism. Re-evaluation of the phenotype of Vpu phosphorylation mutants and naturally occurring allelic variants reveals that the requirement for the Vpu phosphoserine motif in tetherin antagonism is dissociable from SCFβTRCP1/2 and ESCRT-dependent tetherin degradation. Vpu phospho-mutants phenocopy ExxxLV mutants, and can be rescued by direct clathrin interaction in the absence of SCFβTRCP1/2 recruitment. Moreover, we demonstrate physical interaction between Vpu and AP-1 or AP-2 in cells. This requires Vpu/tetherin transmembrane domain interactions as well as the ExxxLV motif. Importantly, it also requires the Vpu phosphoserine motif and adjacent acidic residues. Taken together these data explain the discordance between the role of SCFβTRCP1/2 and Vpu phosphorylation in tetherin antagonism, and indicate that phosphorylation of Vpu in Vpu/tetherin complexes regulates promiscuous recruitment of adaptors, implicating clathrin-dependent sorting as an essential first step in tetherin antagonism.

Indexed as

Adaptor Proteins, Vesicular TransportAntigens, CDBone Marrow Stromal Antigen 2CD4-Positive T-LymphocytesClathrinFlow CytometryFluorescent Antibody TechniqueGPI-Linked ProteinsHEK293 CellsHIV-1Human Immunodeficiency Virus ProteinsHumansImmunoprecipitationPhosphorylationProtein BindingProtein TransportAdaptor Proteins, Vesicular TransportAntigens, CDBone Marrow Stromal Antigen 2BST2 protein, humanClathrinGPI-Linked ProteinsHuman Immunodeficiency Virus ProteinsRNA, Small InterferingSerineViral Regulatory and Accessory ProteinsViroporin Proteinsvpu protein, Human immunodeficiency virus 1

Identifiers

PMID26317613
PMCPMC4552633
OpenAlexW1625411473

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.