ArticleJournal of virology2015
Nef Proteins from HIV-1 Elite Controllers Are Inefficient at Preventing Antibody-Dependent Cellular Cytotoxicity.
Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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
61 citing papers in PubMed, 78 citations in OpenAlex.
- mGem: Opening Env and harnessing NK cell effector functions to eliminate HIV-1-infected cells.mBio · 2026Review
- Molecular parameters governing antibody FcγR signaling and effector functions in the context of HIV envelope.Cell reports · 2025Article
- HIV controllers: hope for a functional cure.Frontiers in immunology · 2025Review
- Article
- Article
- Article
- Article
- Advances in HIV Research Using Mass Cytometry.Current HIV/AIDS reports · 2023Review
- In-Depth Characterization of Full-Length Archived Viral Genomes after Nine Years of Posttreatment HIV Control.Microbiology spectrum · 2023Article
- Small CD4 mimetics sensitize HIV-1-infected macrophages to antibody-dependent cellular cytotoxicity.Cell reports · 2023Article
- Nef enhances HIV-1 replication and infectivity independently of SERINC5 in CEM T cells.Virology · 2023Article
- HIV-1 Vpu restricts Fc-mediated effector functions in vivo.Cell reports · 2022Article
- Characterization of Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Variants Selected for Resistance to a CD4-Mimetic Compound.Journal of virology · 2022Article
- Mechanism of Viral Suppression among HIV Elite Controllers and Long-Term Nonprogressors in Nigeria and South Africa.Viruses · 2022Review
- The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells.The Journal of clinical investigation · 2022Article
- Detection of the HIV-1 Accessory Proteins Nef and Vpu by Flow Cytometry Represents a New Tool to Study Their Functional Interplay within a Single Infected CD4Journal of virology · 2022Article
- Selection of HIV Envelope Strains for Standardized Assessments of Vaccine-Elicited Antibody-Dependent Cellular Cytotoxicity-Mediating Antibodies.Journal of virology · 2022Article
- Non-neutralizing antibodies targeting the immunogenic regions of HIV-1 envelope reduce mucosal infection and virus burden in humanized mice.PLoS pathogens · 2022Article
- Evolution of Antibodies to Native Trimeric Envelope and Their Fc-Dependent Functions in Untreated and Treated Primary HIV Infection.Journal of virology · 2021Article
- Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledImpairment of Nef function, including reduced CD4 downregulation, was described in a subset of HIV-1-infected individuals that control viral replication without antiretroviral treatment (elite controllers [EC]). Elimination of HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC) requires the presence of envelope glycoproteins (Env) in the CD4-bound conformation, raising the possibility that accumulating CD4 at the surface of virus-infected cells in EC could interact with Env and thereby sensitize these cells to ADCC. We observed a significant increase in the exposure of Env epitopes targeted by ADCC-mediating antibodies at the surface of cells expressing Nef isolates from EC; this correlated with enhanced susceptibility to ADCC. Altogether, our results suggest that enhanced susceptibility of HIV-1-infected cells to ADCC may contribute to the EC phenotype. IMPORTANCE: Nef clones derived from elite controllers (EC) have been shown to be attenuated for CD4 downregulation; how this contributes to the nonprogressor phenotype of these infected individuals remains uncertain. Increasing evidence supports a role for HIV-specific antibody-dependent cellular cytotoxicity (ADCC) in controlling viral infection and replication. Here, we show that residual CD4 left at the surface of cells expressing Nef proteins isolated from ECs are sufficient to allow Env-CD4 interaction, leading to increased exposure of Env CD4-induced epitopes and increased susceptibility of infected cells to ADCC. Our results suggest that ADCC might be an active immune mechanism in EC that helps to maintain durable suppression of viral replication and low plasma viremia level in this rare subset of infected individuals. Therefore, targeting Nef's ability to downregulate CD4 could render HIV-1-infected cells susceptible to ADCC and thus have therapeutic utility.
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.