Evidence map›Paper›PMID 29970186›Full record

ArticleRetrovirology2018

Global phosphoproteomics of CCR5-tropic HIV-1 signaling reveals reprogramming of cellular protein production pathways and identifies p70-S6K1 and MK2 as HIV-responsive kinases required for optimal infection of CD4+ T cells.

Danica D Wiredja, Caroline O Tabler, Daniela M Schlatzer, Ming Li, Mark R Chance, John C Tilton

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Retrovirology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
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 1 institution in 1 country.

Danica D WiredjaDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
Caroline O TablerDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
Daniela M SchlatzerDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
Ming LiDepartment of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
Mark R ChanceDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
John C TiltonDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA. jct63@case.edu.ORCID 0000-0002-4218-5870
Case Western Reserve University · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
WG3: HIV, Co-infections and Co-morbiditiesP30AI036219 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI Sharon L. Hillier, JONATHAN KARN · 1994 to 2026
$50.0M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4M
NRSA Training CoreTL1TR002549 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 2018 to 2022
$2.9M
Phospho Proteomics Alzheimers SupplementR01GM117208 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI CHANCE, MARK R · 2016 to 2018
$1.4M
Detection of Latent HIV Infection Using Selective Reaction Monitoring Mass SpectrR21AI113148 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI TILTON, JOHN CHRISTIAN · 2014 to 2015
$436k
Clinical and Translational Science Collaborative of Cleveland 4UL1TR000439National Institute of Allergy and Infectious Diseases AI036219National Institute of Allergy and Infectious Diseases R21AI113148NCATS NIH HHS TL1 TR002549NCATS NIH HHS UL1 TR000439NIAID NIH HHS P30 AI036219NIAID NIH HHS R21 AI113148NIGMS NIH HHS R01 GM117208NIGMS NIH HHS R01GM117208NIGMS NIH HHS T32 GM007250
6 · The paper itself

Abstract

backgroundViral reprogramming of host cells enhances replication and is initiated by viral interaction with the cell surface. Upon human immunodeficiency virus (HIV) binding to CD4+ T cells, a signal transduction cascade is initiated that reorganizes the actin cytoskeleton, activates transcription factors, and alters mRNA splicing pathways.

methodsWe used a quantitative mass spectrometry-based phosphoproteomic approach to investigate signal transduction cascades initiated by CCR5-tropic HIV, which accounts for virtually all transmitted viruses and the vast majority of viruses worldwide.

resultsCCR5-HIV signaling induced significant reprogramming of the actin cytoskeleton and mRNA splicing pathways, as previously described. In addition, CCR5-HIV signaling induced profound changes to the mRNA transcription, processing, translation, and post-translational modifications pathways, indicating that virtually every stage of protein production is affected. Furthermore, we identified two kinases regulated by CCR5-HIV signaling-p70-S6K1 (RPS6KB1) and MK2 (MAPKAPK2)-that were also required for optimal HIV infection of CD4+ T cells. These kinases regulate protein translation and cytoskeletal architecture, respectively, reinforcing the importance of these pathways in viral replication. Additionally, we found that blockade of CCR5 signaling by maraviroc had relatively modest effects on CCR5-HIV signaling, in agreement with reports that signaling by CCR5 is dispensable for HIV infection but in contrast to the critical effects of CXCR4 on cortical actin reorganization.

conclusionsThese results demonstrate that CCR5-tropic HIV induces significant reprogramming of host CD4+ T cell protein production pathways and identifies two novel kinases induced upon viral binding to the cell surface that are critical for HIV replication in host cells.

Indexed as

Signal TransductionCD4-Positive T-LymphocytesCytoskeletonHIV-1HIV InfectionsHost-Pathogen InteractionsHumansImmunologic MemoryIntracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2PhosphoproteinsProtein Serine-Threonine KinasesProteomicsReceptors, CCR5Receptors, CXCR4Ribosomal Protein S6 Kinases, 70-kDaCXCR4 protein, humanIntracellular Signaling Peptides and ProteinsMAP-Kinase-Activated Kinase 2PhosphoproteinsProtein Serine-Threonine KinasesReceptors, CCR5Receptors, CXCR4ribosomal protein S6 kinase, 70kD, polypeptide 1Ribosomal Protein S6 Kinases, 70-kDaCCR5HIV-1PhosphoproteomicsPost-translational modificationsSignalingSplicingTranscriptionTranslation

Identifiers

PMID29970186
PMCPMC6029029
OpenAlexW2810988375

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.