ArticleJournal of virology2012
Efficient Nef-mediated downmodulation of TCR-CD3 and CD28 is associated with high CD4+ T cell counts in viremic HIV-2 infection.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- The Confluence of HIV-1 and HIV-2: Implications for Disease Progression and Insights for Therapy.International journal of microbiology · 2025Review
- Pro-inflammatory feedback loops define immune responses to pathogenic Lentivirus infection.Genome medicine · 2024Article
- Genotypic and Phenotypic Characterization of Replication-Competent HIV-2 Isolated from Controllers and Progressors.Viruses · 2023Article
- Article
- Substitutions in Nef That Uncouple Tetherin and SERINC5 Antagonism Impair Simian Immunodeficiency Virus Replication in Primary Rhesus Macaque Lymphocytes.Journal of virology · 2022Article
- Selective Disruption of SERINC5 Antagonism by Nef Impairs SIV Replication in Primary CD4Journal of virology · 2021Article
- Loss of Nef-mediated CD3 down-regulation in the HIV-1 lineage increases viral infectivity and spread.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structure of HIV-2 Nef Reveals Features Distinct from HIV-1 Involved in Immune Regulation.iScience · 2020Article
- Tetherin downmodulation by SIVmac Nef lost with the H196Q escape variant is restored by an upstream variant.PloS one · 2020Article
- How HIV Nef Proteins Hijack Membrane Traffic To Promote Infection.Journal of virology · 2019Review
- HIV-2 Depletes CD4 T Cells through Pyroptosis despite Vpx-Dependent Degradation of SAMHD1.Journal of virology · 2019Article
- Preadaptation of Simian Immunodeficiency Virus SIVsmm Facilitated Env-Mediated Counteraction of Human Tetherin by Human Immunodeficiency Virus Type 2.Journal of virology · 2018Article
- SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue.PLoS pathogens · 2018Article
- Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity.Nature communications · 2018Article
- Maintenance of AP-2-Dependent Functional Activities of Nef Restricts Pathways of Immune Escape from CD8 T Lymphocyte Responses.Journal of virology · 2018Article
- HLA-DQB1*06 and breadth of Nef core region-specific T-cell response are associated with slow disease progression in antiretroviral therapy-naive Chinese HIV-1 subtype B patients.Human vaccines & immunotherapeutics · 2017Article
- Primate Lentiviruses Modulate NF-κB Activity by Multiple Mechanisms to Fine-Tune Viral and Cellular Gene Expression.Frontiers in microbiology · 2017Review
- The KT Jeang Retrovirology prize 2016: Frank Kirchhoff.Retrovirology · 2016Article
- Acute Viral Escape Selectively Impairs Nef-Mediated Major Histocompatibility Complex Class I Downmodulation and Increases Susceptibility to Antiviral T Cells.Journal of virology · 2016Article
- Lentiviral Nef proteins manipulate T cells in a subset-specific manner.Journal of virology · 2015Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 5 countries.
Funding
Abstract
The role of the multifunctional accessory Nef protein in the immunopathogenesis of HIV-2 infection is currently poorly understood. Here, we performed comprehensive functional analyses of 50 nef genes from 21 viremic (plasma viral load, >500 copies/ml) and 16 nonviremic (<500) HIV-2-infected individuals. On average, nef alleles from both groups were equally active in modulating CD4, TCR-CD3, CD28, MHC-I, and Ii cell surface expression and in enhancing virion infectivity. Thus, many HIV-2-infected individuals efficiently control the virus in spite of efficient Nef function. However, the potency of nef alleles in downmodulating TCR-CD3 and CD28 to suppress the activation and apoptosis of T cells correlated with high numbers of CD4(+) T cells in viremic patients. No such correlations were observed in HIV-2-infected individuals with undetectable viral load. Further functional analyses showed that the Nef-mediated downmodulation of TCR-CD3 suppressed the induction of Fas, Fas-L, PD-1, and CTLA-4 cell surface expression as well as the secretion of gamma interferon (IFN-γ) by primary CD4(+) T cells. Moreover, we identified a single naturally occurring amino acid variation (I132T) in the core domain of HIV-2 Nef that selectively disrupts its ability to downmodulate TCR-CD3 and results in functional properties highly reminiscent of HIV-1 Nef proteins. Taken together, our data suggest that the efficient Nef-mediated downmodulation of TCR-CD3 and CD28 help viremic HIV-2-infected individuals to maintain normal CD4(+) T cell homeostasis by preventing T cell activation and by suppressing the induction of death receptors that may affect the functionality and survival of both virally infected and uninfected bystander 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.