ArticleScientific reports2016
HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 68 citations in OpenAlex.
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Host Cell Virus Interactions: Molecular Mechanisms, Immune Modulation, Viral Pathogenesis, and Emerging Therapeutic Targets.Viruses · 2026Review
- Chimeric antigen receptor T‑cell therapy in chronic viral infections: a review.Journal of translational medicine · 2026Review
- NF-κB-dependent and independent inflammatory responses during acute HIV-1 infection in a model of human microglia.Frontiers in immunology · 2026Article
- Ancestral reconstruction supports that loss of Nef-mediated T cell modulation coincided with the emergence of pathogenic lentiviruses.Journal of virology · 2025Article
- Beyond Viral Assembly: The Emerging Role of HIV-1 p17 in Vascular Inflammation and Endothelial Dysfunction.International journal of molecular sciences · 2025Review
- Viral manipulation of the HLA class I antigen processing and presentation pathway.Frontiers in immunology · 2025Review
- Involvement of Human Cellular Proteins and Structures in Realization of the HIV Life Cycle: A Comprehensive Review, 2024.Viruses · 2024Review
- Nef defect attenuates HIV viremia and immune dysregulation in the bone marrow-liver-thymus-spleen (BLTS) humanized mouse model.Virology · 2024Article
- PACS-1 Interacts with TRPC3 and ESyt1 to Mediate Protein Trafficking while Promoting SOCE and Cooperatively Regulating Hormone Secretion.ACS omega · 2024Article
- SARS-CoV-2 NSP5 antagonizes MHC II expression by subverting histone deacetylase 2.Journal of cell science · 2024Article
- Molecular disparities in colorectal cancers of White Americans, Alabama African Americans, and Oklahoma American Indians.NPJ precision oncology · 2023Article
- HIV-Host Cell Interactions.Cells · 2023Review
- Atlantic cod (Frontiers in cell and developmental biology · 2023Article
- HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS.Pathogens & immunity · 2023Article
- The Persistence of HIV Diversity, Transcription, and Nef Protein in Kaposi's Sarcoma Tumors during Antiretroviral Therapy.Viruses · 2022Article
- The deciphering of the immune cells and marker signature in COVID-19 pathogenesis: An update.Journal of medical virology · 2022Review
- Self-assembly and structure of a clathrin-independent AP-1:Arf1 tubular membrane coat.Science advances · 2022Article
- The Phosphofurin Acidic Cluster Sorting Protein 2 (PACS-2) E209K Mutation Responsible for PACS-2 Syndrome Increases Susceptibility to Apoptosis.ACS omega · 2022Article
- 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
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
A defining characteristic of HIV-1 infection is the ability of the virus to persist within the host. Specifically, MHC-I downregulation by the HIV-1 accessory protein Nef is of critical importance in preventing infected cells from cytotoxic T-cell mediated killing. Nef downregulates MHC-I by modulating the host membrane trafficking machinery, resulting in the endocytosis and eventual sequestration of MHC-I within the cell. In the current report, we utilized the intracellular protein-protein interaction reporter system, bimolecular fluorescence complementation (BiFC), in combination with super-resolution microscopy, to track the Nef/MHC-I interaction and determine its subcellular localization in cells. We demonstrate that this interaction occurs upon Nef binding the MHC-I cytoplasmic tail early during endocytosis in a Rab5-positive endosome. Disruption of early endosome regulation inhibited Nef-dependent MHC-I downregulation, demonstrating that Nef hijacks the early endosome to sequester MHC-I within the cell. Furthermore, super-resolution imaging identified that the Nef:MHC-I BiFC complex transits through both early and late endosomes before ultimately residing at the trans-Golgi network. Together we demonstrate the importance of the early stages of the endocytic network in the removal of MHC-I from the cell surface and its re-localization within the cell, which allows HIV-1 to optimally evade host immune responses.
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