ArticlePloS one2012
HIV-1 Vpr triggers mitochondrial destruction by impairing Mfn2-mediated ER-mitochondria interaction.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 103 citations in OpenAlex.
- Broadband electronic resonance coherent anti-Stokes/Stokes Raman scattering microscopy.Science advances · 2026Article
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- HIV infection and immunosenescence: challenges and intervention strategies.BMC medicine · 2025Review
- Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities.Pathogens (Basel, Switzerland) · 2025Review
- Increased ROS levels activate AMPK-ULK1-mediated mitophagy to promote pseudorabies virus replication.Veterinary research · 2025Article
- Comparative immunological study of Plasmodium knowlesi infections in humans and macaques: insights into cytokine dynamics.Malaria journal · 2025Article
- Review
- Review
- Role of mitochondria-associated membranes (MAMs) in inflammatory signaling: implications for acute lung injury pathogenesis.Frontiers in cell and developmental biology · 2025Review
- Mitochondrial DNA damage in HIV infection: a mechanistic driver of immunometabolic dysfunction and chronic inflammation.Frontiers in immunology · 2025Review
- Crosstalk between Dysfunctional Mitochondria and Proinflammatory Responses during Viral Infections.International journal of molecular sciences · 2024Review
- Targeting mitochondrial quality control: new therapeutic strategies for major diseases.Military Medical Research · 2024Review
- CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X.Viruses · 2024Review
- ROS Chronicles in HIV Infection: Genesis of Oxidative Stress, Associated Pathologies, and Therapeutic Strategies.Current issues in molecular biology · 2024Review
- HIV-1 and methamphetamine co-treatment in primary human astrocytes: TAARgeting ER/UPR dysfunction.NeuroImmune pharmacology and therapeutics · 2024Article
- Connection Between HIV and Mitochondria in Cardiovascular Disease and Implications for Treatments.Circulation research · 2024Review
- HIV-1 Vpr Functions in Primary CD4Viruses · 2024Review
- Viral regulation of organelle membrane contact sites.PLoS biology · 2024Article
- Apoptosis dysfunction: unravelling the interplay between ZBP1 activation and viral invasion in innate immune responses.Cell communication and signaling : CCS · 2024Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus 1 (HIV-1) viral protein R (Vpr) has been shown to induce host cell death by increasing the permeability of mitochondrial outer membrane (MOM). The mechanism underlying the damage to the mitochondria by Vpr, however, is not clearly illustrated. In this study, Vpr that is introduced, via transient transfection or lentivirus infection, into the human embryonic kidney cell line HEK293, human CD4(+) T lymphoblast cell line SupT1, or human primary CD4(+) T cells serves as the model system to study the molecular mechanism of Vpr-mediated HIV-1 pathogenesis. The results show that Vpr injures MOM and causes a loss in membrane potential (MMP) by posttranscriptionally reducing the expression of mitofusin 2 (Mfn2) via VprBP-DDB1-CUL4A ubiquitin ligase complex, gradually weakening MOM, and increasing mitochondrial deformation. Vpr also markedly decreases cytoplasmic levels of dynamin-related protein 1 (DRP1) and increases bulging in mitochondria-associated membranes (MAM), the specific regions of endoplasmic reticulum (ER) which form physical contacts with the mitochondria. Overexpression of Mfn2 and DRP1 significantly decreased the loss of MMP and apoptotic cell death caused by Vpr. Furthermore, by employing time-lapse confocal fluorescence microscopy, we identify the transport of Vpr protein from the ER, via MAM to the mitochondria. Taken together, our results suggest that Vpr-mediated cellular damage may occur on an alternative protein transport pathway from the ER, via MAM to the mitochondria, which are modulated by Mfn2 and DRP1.
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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.