Evidence map›Paper›PMID 24415754›Full record

ArticleThe Journal of biological chemistry2014

HIV-1 triggers WAVE2 phosphorylation in primary CD4 T cells and macrophages, mediating Arp2/3-dependent nuclear migration.

Mark Spear, Jia Guo, Amy Turner, Dongyang Yu, Weifeng Wang, Beatrix Meltzer, Sijia He, Xiaohua Hu, Hong Shang, Jeffrey Kuhn and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
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

24 citing papers in PubMed, 38 citations in OpenAlex.

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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

11 authors at 4 institutions in 2 countries.

Mark SpearNational Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
Jia GuoNational Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
Amy TurnerNational Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
Dongyang YuNational Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
Weifeng WangNational Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
Beatrix MeltzerNational Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110.
Sijia HeKey Laboratory of Immunology of AIDS, Ministry of Health, the First Affiliated Hospital, China Medical University, Shenyang, Liaoning province 110001, China.
Xiaohua HuDepartment of Biological Sciences, Virginia Tech, Blacksburg, Virginia 24060.
Hong ShangKey Laboratory of Immunology of AIDS, Ministry of Health, the First Affiliated Hospital, China Medical University, Shenyang, Liaoning province 110001, China.
Jeffrey KuhnDepartment of Biological Sciences, Virginia Tech, Blacksburg, Virginia 24060.
Yuntao WuNational Center for Biodefense and Infectious Diseases, Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110. Electronic address: ywu8@gmu.edu.
George Mason University · USVirginia Tech · USChina Medical University · CNFirst Hospital of China Medical University · CN

Funding

Validation of the Rev-dependent vector for targeting SIV macrophage reservoirsR01MH102144 · NIMH · GEORGE MASON UNIVERSITY · PI WU, YUNTAO · 2014 to 2018
$3.3M
Regulation of Cofilin in HIV-1 Infection of Human CD4 T CellsR01AI081568 · NIAID · GEORGE MASON UNIVERSITY · PI WU, YUNTAO · 2009 to 2012
$1.2M
Development of an HIV Rev-dependent dual-reporter cell for anti-HIV drug screeninR03AI093157 · NIAID · GEORGE MASON UNIVERSITY · PI WU, YUNTAO · 2011 to 2012
$142k
NIAID NIH HHS 1R01AI081568NIAID NIH HHS 1R03AI093157NIAID NIH HHS R01 AI081568NIAID NIH HHS R03 AI093157NIMH NIH HHS R01 MH102144
6 · The paper itself

Abstract

The human immunodeficiency virus type 1 (HIV-1) initiates receptor signaling and early actin dynamics during viral entry. This process is required for viral infection of primary targets such as resting CD4 T cells. WAVE2 is a component of a multiprotein complex linking receptor signaling to dynamic remodeling of the actin cytoskeleton. WAVE2 directly activates Arp2/3, leading to actin nucleation and filament branching. Although several bacterial and viral pathogens target Arp2/3 for intracellular mobility, it remains unknown whether HIV-1 actively modulates the Arp2/3 complex through virus-mediated receptor signal transduction. Here we report that HIV-1 triggers WAVE2 phosphorylation at serine 351 through gp120 binding to the chemokine coreceptor CXCR4 or CCR5 during entry. This phosphorylation event involves both Gαi-dependent and -independent pathways, and is conserved both in X4 and R5 viral infection of resting CD4 T cells and primary macrophages. We further demonstrate that inhibition of WAVE2-mediated Arp2/3 activity through stable shRNA knockdown of Arp3 dramatically diminished HIV-1 infection of CD4 T cells, preventing viral nuclear migration. Inhibition of Arp2/3 through a specific inhibitor, CK548, also drastically inhibited HIV-1 nuclear migration and infection of CD4 T cells. Our results suggest that Arp2/3 and the upstream regulator, WAVE2, are essential co-factors hijacked by HIV for intracellular migration, and may serve as novel targets to prevent HIV transmission.

Indexed as

Actin-Related Protein 2-3 ComplexCD4-Positive T-LymphocytesCell NucleusGene Knockdown TechniquesHeLa CellsHIV-1HIV InfectionsHumansMacrophagesPhosphorylationRNA, Small InterferingVirus ReplicationWiskott-Aldrich Syndrome Protein FamilyActin-Related Protein 2-3 ComplexRNA, Small InterferingWASF2 protein, humanWiskott-Aldrich Syndrome Protein FamilyArp2/3CCR5CD4HIV-1ImmunologyMicrobiologySignal TransductionVirologyWav2

Identifiers

PMID24415754
PMCPMC3945356
OpenAlexW1968015724

What Socratic 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 Socratic graph.