Evidence map›Paper›PMID 28114951›Full record

ArticleRetrovirology2017

HIV signaling through CD4 and CCR5 activates Rho family GTPases that are required for optimal infection of primary CD4+ T cells.

Mark B Lucera, Zach Fleissner, Caroline O Tabler, Daniela M Schlatzer, Zach Troyer, John C Tilton

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.7field-weighted citation impact, top 36% 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

20 citing papers in PubMed, 27 citations in OpenAlex.

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  4. Myosin IXB protects immune cells from virus infection.The Journal of general virology · 2025
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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.

Mark B LuceraDivision of Infectious Diseases, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA.
Zach FleissnerDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, BRB 919, Cleveland, OH, 44106, USA.
Caroline O TablerDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, BRB 919, Cleveland, OH, 44106, USA.
Daniela M SchlatzerDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, BRB 919, Cleveland, OH, 44106, USA.
Zach TroyerDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, BRB 919, Cleveland, OH, 44106, USA.
John C TiltonDepartment of Nutrition, Center for Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, BRB 919, Cleveland, OH, 44106, USA. jct63@case.edu.ORCID 0000-0002-4218-5870
Case Western Reserve University · USUniversity of Colorado Anschutz Medical Campus · US

Funding

WG3: HIV, Co-infections and Co-morbiditiesP30AI036219 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI Sharon L. Hillier, JONATHAN KARN · 1994 to 2026
$50.0M
GRADUATE TRAINING IN CELLULAR AND MOLECULAR BIOLOGYT32GM008056 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI DIEHL, JOHN ALAN, SNIDER, MARTIN D · 1985 to 2019
$7.1M
Enhancement of HIV transmission by hormones and bacterial metabolitesR01HD077886 · NICHD · CASE WESTERN RESERVE UNIVERSITY · PI TILTON, JOHN CHRISTIAN · 2013 to 2017
$2.2M
Training Program in HIV CureT32AI127201 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI LEVINE, ALAN DAVID · 2016 to 2020
$919k
NIAID NIH HHS P30 AI036219NIAID NIH HHS T32 AI127201NICHD NIH HHS R01 HD077886NIGMS NIH HHS T32 GM008056
6 · The paper itself

Abstract

backgroundHIV-1 hijacks host cell machinery to ensure successful replication, including cytoskeletal components for intracellular trafficking, nucleoproteins for pre-integration complex import, and the ESCRT pathway for assembly and budding. It is widely appreciated that cellular post-translational modifications (PTMs) regulate protein activity within cells; however, little is known about how PTMs influence HIV replication. Previously, we reported that blocking deacetylation of tubulin using histone deacetylase inhibitors promoted the kinetics and efficiency of early post-entry viral events. To uncover additional PTMs that modulate entry and early post-entry stages in HIV infection, we employed a flow cytometric approach to assess a panel of small molecule inhibitors on viral fusion and LTR promoter-driven gene expression.

resultsWhile viral fusion was not significantly affected, early post-entry viral events were modulated by drugs targeting multiple processes including histone deacetylation, methylation, and bromodomain inhibition. Most notably, we observed that inhibitors of the Rho GTPase family of cytoskeletal regulators-including RhoA, Cdc42, and Rho-associated kinase signaling pathways-significantly reduced viral infection. Using phosphoproteomics and a biochemical GTPase activation assay, we found that virion-induced signaling via CD4 and CCR5 activated Rho family GTPases including Rac1 and Cdc42 and led to widespread modification of GTPase signaling-associated factors.

conclusionsTogether, these data demonstrate that HIV signaling activates members of the Rho GTPase family of cytoskeletal regulators that are required for optimal HIV infection of primary CD4+ T cells.

Indexed as

Signal TransductionCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedHIVHost-Pathogen InteractionsHumansReceptors, CCR5rho GTP-Binding ProteinsVirus IntegrationVirus InternalizationCCR5 protein, humanCD4 AntigensReceptors, CCR5rho GTP-Binding ProteinsCdc42HIV-1Rho GTPasesROCKSmall molecule screenViral infection

Identifiers

PMID28114951
PMCPMC5259950
OpenAlexW2580427763

What OpenQuestion holds

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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.