ArticleRetrovirology2010
Expression of Nef from unintegrated HIV-1 DNA downregulates cell surface CXCR4 and CCR5 on T-lymphocytes.
Article in Retrovirology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Versatile HIV Rev-dependent reporter cell system for stringent and sensitive quantification of viral reservoirs, neutralizing antibodies, and restriction factors.Retrovirology · 2026Article
- Dynamics of natural and pharmacologic control of an SIV variant with an envelope trafficking defect.The Journal of experimental medicine · 2026Article
- CXCR4-modification enhances CAR-T efficacy by improving tumor tracking and bone marrow homing in B-cell malignancies.Signal transduction and targeted therapy · 2026Article
- Versatile HIV Rev-dependent reporter cell system for stringent and sensitive quantification of viral reservoirs, neutralizing antibodies, and restriction factors.bioRxiv : the preprint server for biology · 2025Article
- Assembly of CCR5 with gp120 inhibits the HIV infectivity specifically in T cells.Scientific reports · 2025Article
- Neutron Reflectometry and Molecular Simulations Demonstrate HIV-1 Nef Homodimer Formation on Model Lipid Bilayers.Journal of molecular biology · 2023Article
- HIV Preintegration Transcription and Host Antagonism.Current HIV research · 2023Article
- Article
- Two lymphoid cell lines potently silence unintegrated HIV-1 DNAs.Retrovirology · 2022Article
- Nef homodimers down-regulate SERINC5 by AP-2-mediated endocytosis to promote HIV-1 infectivity.The Journal of biological chemistry · 2020Article
- A comparative analysis of unintegrated HIV-1 DNA measurement as a potential biomarker of the cellular reservoir in the blood of patients controlling and non-controlling viral replication.Journal of translational medicine · 2020Article
- HIV-1 Nef dimers short-circuit immune receptor signaling by activating Tec-family kinases at the host cell membrane.The Journal of biological chemistry · 2020Article
- Tat IRES modulator of tat mRNA (TIM-TAM): a conserved RNA structure that controls Tat expression and acts as a switch for HIV productive and latent infection.Nucleic acids research · 2020Article
- Ubiquitin E3 Ligase c-Cbl Is a Host Negative Regulator of Nef Protein of HIV-1.Frontiers in microbiology · 2020Article
- Tat controls transcriptional persistence of unintegrated HIV genome in primary human macrophages.Virology · 2018Article
- Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation.PLoS pathogens · 2017Article
- Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1.Journal of virology · 2017Article
- Underlying mechanisms of HIV-1 latency.Virus genes · 2017Review
- Cell-based Fluorescence Complementation Reveals a Role for HIV-1 Nef Protein Dimerization in AP-2 Adaptor Recruitment and CD4 Co-receptor Down-regulation.The Journal of biological chemistry · 2017Article
- Distribution and fate of HIV-1 unintegrated DNA species: a comprehensive update.AIDS research and therapy · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTranscription of HIV-1 cDNA prior to, or in the absence of, integration leads to synthesis of all classes of viral RNA transcripts. Yet only a limited range of viral proteins, including Nef, are translated in this context. Nef expression from unintegrated HIV-1 DNA has been shown to reduce cell surface CD4 levels in T-cells. We wished to determine whether Nef expressed from unintegrated DNA was also able to downregulate the chemokine coreceptors CXCR4 and CCR5.Viral integration was blocked through use of an inactive integrase or by using the integrase inhibitor raltegravir. Infected cells bearing unintegrated DNA were assayed by flow cytometry in the GFP reporter cell line, Rev-CEM, for cell surface levels of CD4, CXCR4 and CCR5.
resultsIn cells bearing only unintegrated HIV-1 DNA, we found that surface levels of CXCR4 were significantly reduced, while levels of CCR5 were also diminished, but not to the extent of CXCR4. We also confirmed the downregulation of CD4. Similar patterns of results were obtained with both integrase-deficient virus or with wild-type infections of cells treated with raltegravir. The Alu-HIV qPCR assay that we used for detection of proviral DNA did not detect any integrated viral DNA.
conclusionsOur results demonstrate that Nef can be expressed from unintegrated DNA at functionally relevant levels and suggest a role for Nef in downregulation of CXCR4 and CCR5. These findings may help to explain how downregulation of CXCR4, CCR5 and CD4 might restrict superinfection and/or prevent signal transduction involving HIV-1 infected cells.
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Registered trials
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.