ArticleRetrovirology2009
Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivo.
Article in Retrovirology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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.
Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Modeling HIV infection, treatment, rebound, and intervention in human immune organoids.bioRxiv : the preprint server for biology · 2026Article
- Activation-neutral gene editing of tonsillar CD4 T cells for functional studies in human ex vivo tonsil cultures.Cell reports methods · 2024Article
- Modulation of the autophagic pathway inhibits HIV-1 infection in human lymphoid tissue cultured ex vivo.Scientific reports · 2022Article
- 3D Tissue Explant and Single-Cell Suspension Organoid Culture Systems for Ex Vivo Drug Testing on Human Tonsil-Derived T Follicular Helper Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Inhibition of polo-like kinase 1 (PLK1) facilitates reactivation of gamma-herpesviruses and their elimination.PLoS pathogens · 2021Article
- Contact-dependent inhibition of HIV-1 replication inCell reports. Medicine · 2021Article
- Nef Obtained from Individuals with HIV-1 Vary in Their Ability to Antagonize SERINC3- and SERINC5-Mediated HIV-1 Restriction.Viruses · 2021Article
- HIV-1 infection of CD4 T cells impairs antigen-specific B cell function.The EMBO journal · 2020Article
- Complex human adenoid tissue-based ex vivo culture systems reveal anti-inflammatory drug effects on germinal center T and B cells.EBioMedicine · 2020Article
- Human FCHO1 deficiency reveals role for clathrin-mediated endocytosis in development and function of T cells.Nature communications · 2020Article
- Multifunctional Roles of the N-Terminal Region of HIV-1Journal of virology · 2019Article
- Impact of HIV-1 subtype and Korean Red Ginseng on AIDS progression: comparison of subtype B and subtype D.Journal of ginseng research · 2019Article
- Spotlight on HIV-1 Nef: SERINC3 and SERINC5 Identified as Restriction Factors Antagonized by the Pathogenesis Factor.Viruses · 2015Article
- In vivo analysis of Nef's role in HIV-1 replication, systemic T cell activation and CD4(+) T cell loss.Retrovirology · 2015Article
- Adding new dimensions: towards an integrative understanding of HIV-1 spread.Nature reviews. Microbiology · 2014Review
- Restrictions to HIV-1 replication in resting CD4+ T lymphocytes.Cell research · 2013Review
- HIV-1 Nef: a multifaceted modulator of T cell receptor signaling.Cell communication and signaling : CCS · 2012Article
- Nef functions in BLT mice to enhance HIV-1 replication and deplete CD4+CD8+ thymocytes.Retrovirology · 2012Article
- Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function.Retrovirology · 2012Article
- Review: micronutrient selenium deficiency influences evolution of some viral infectious diseases.Biological trace element research · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHIV-1 Nef critically contributes to AIDS in part by augmenting virus titers in infected individuals. Analyzing which of Nef's activities contribute to HIV pathogenesis has been hampered by the lack of a cell culture model in which Nef exerts pronounced effects on HIV replication. The human lymphoid aggregate culture (HLAC) from tonsil maintains the cell populations and cytokine milieu found in vivo, supports a productive infection without exogenous stimulation, and Nef contributes to efficient HIV-1 replication as well as CD4+ T cell depletion in this experimental ex vivo-model.
resultsTo identify determinants in Nef that mediate these activities, we infected HLAC with a panel of isogenic HIV-1NL4-3 strains that encode for well-characterized mutants of HIV-1SF2 Nef. Determination of HIV-1 replication revealed that enhancement of the virus spread by Nef is governed by a complex set of protein interaction surfaces. In contrast, increased CD4+ T lymphocyte depletion depended on only two protein interaction surfaces in Nef that mediate either downregulation of cell surface CD4 or interaction with the NAKC signalosome. Consistently, in HLAC from 9 out of 14 donors, Nef enhanced CD4+ T cell depletion in the absence of a significant effect on virus replication. Moreover, our results suggest that this Nef-dependent enhancement in depletion occurred predominately in uninfected bystander CD4+ T cells.
conclusionOur findings suggest that Nef facilitates depletion of CD4+ T lymphocytes in HIV-1-infected lymphoid tissue ex vivo by increasing the pool of productively infected cells and by sensitizing bystander cells for killing. This ability might contribute to Nef's pathogenic potential in vivo.
Indexed as
Identifiers
What OpenQuestion holds
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.