Evidence map›Paper›PMID 18453587›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2008

Signaling mechanism of HIV-1 gp120 and virion-induced IL-1beta release in primary human macrophages.

Ricky Cheung, Vipa Ravyn, Lingshu Wang, Andrzej Ptasznik, Ronald G Collman

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
2.1field-weighted citation impact, top 13% 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

55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026
    Review
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  13. Emerging Role of Nef in the Development of HIV Associated Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021
    Review
  14. Review
  15. CCR5 is a required signaling receptor for macrophage expression of inflammatory genes in response to viral double-stranded RNA.American journal of physiology. Regulatory, integrative and comparative physiology · 2019
    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

5 authors at 2 institutions in 1 country.

Ricky CheungPulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Vipa Ravyn
Lingshu Wang
Andrzej Ptasznik
Ronald G Collman
Pulmonary and Allergy Associates · USUniversity of Pennsylvania · US

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DAVID S METZGER · 1999 to 2026
$78.6M
SCID HU MODEL FOR HIV INFECTION OF THE CNSP01NS027405 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI GONZALEZ-SCARANO, FRANCISCO · 1989 to 2007
$8.2M
HIV: gp120, Chemokine Receptors &Macrophage ActivationR01MH061139 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI COLLMAN, RONALD G · 1999 to 2015
$5.2M
Dual-Tropic HIV-1 Strains and Primary Cell InfectionR01AI035502 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI COLLMAN, RONALD G · 1998 to 2009
$2.9M
Molecular and Cellular Biology of HIV EncephalopathyP50NS027405 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI GONZALEZ-SCARANO, FRANCISCO · 2008 to 2009
$2.2M
Crosstalk between oncoprotein and chemokine signalingR01CA108552 · NCI · UNIVERSITY OF PENNSYLVANIA · PI PTASZNIK, ANDRZEJ · 2005 to 2007
$698k
HIV-1 VPR IN INFECTION OF PRIMARY MACROPHAGESR29AI035502 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI COLLMAN, RONALD G · 1994 to 1997
–
NCI NIH HHS CA 108552NCI NIH HHS R01 CA108552NIAID NIH HHS AI 35502NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI035502NIMH NIH HHS MH 061139NIMH NIH HHS R01 MH061139NINDS NIH HHS NS 027405NINDS NIH HHS P01 NS027405
6 · The paper itself

Abstract

HIV-1 envelope glycoprotein gp120 induces, independently of infection, the release of proinflammatory cytokines, including IL-1beta from macrophages, that are implicated in the pathogenesis of HIV-associated dementia. However, the signal transduction pathways involved have not been fully defined. Previously, our laboratory reported that soluble gp120 activates multiple protein kinases in primary human monocyte-derived macrophages, including the Src family kinase Lyn, PI3K, and the focal adhesion-related proline-rich tyrosine kinase Pyk2. In this study we showed that gp120 induces IL-1beta release from macrophages in a time- and concentration-dependent manner through binding to the chemokine receptor CCR5 and coupling to G(i)alpha protein. Using pharmacological inhibitors and small interfering RNA gene knockdown, we demonstrated that concomitant activation of Lyn, Pyk2, and class IA PI3K are required for gp120-induced IL-1beta production. By coimmunoprecipitation and immunofluorescence confocal microscopy, we showed that CCR5 activation by gp120 triggered the assembly of a signaling complex involving endogenous Lyn, PI3K, and Pyk2 and is associated with PI3K and Pyk2 translocation from the cytoplasm to the membrane where they colocalized with Lyn. Finally, we demonstrated that virion-associated gp120 induced similar response, as structurally intact whole virions also triggered IL-1beta release and re-localization of PI3K and Pyk2. This study identifies a novel signaling mechanism for HIV-1-induced IL-1beta production by primary human macrophages that may be involved in the neuropathogenesis of HIV-associated dementia.

Indexed as

AIDS Dementia ComplexFluorescent Antibody TechniqueFocal Adhesion Kinase 2HIV-1HIV Envelope Protein gp120HumansImmunoprecipitationInterleukin-1betaMacrophagesMicroscopy, ConfocalPhosphatidylinositol 3-KinasesReceptors, CCR5RNA, Small InterferingSignal Transductionsrc-Family KinasesVirionFocal Adhesion Kinase 2HIV Envelope Protein gp120Interleukin-1betalyn protein-tyrosine kinasePhosphatidylinositol 3-KinasesReceptors, CCR5RNA, Small Interferingsrc-Family Kinases

Identifiers

PMID18453587
PMCPMC2375537
OpenAlexW1562398556

What OpenQuestion holds

Textmetadata
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.