ArticlePLoS pathogens2019
Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 126 citations in OpenAlex.
- Review
- Hijacking Host Communication: The Central Role of Extracellular Vesicles in Infectious Disease Pathogenesis.Cells · 2026Review
- HIV-1 Nef generates lasting innate immune memory in haematopoietic stem and progenitor cells in vivo.EMBO reports · 2026Article
- Immune non-response despite effective antiretroviral therapy in people living with HIV: A review of potential mechanisms, biomarkers and therapeutic approaches.HIV medicine · 2026Review
- Review
- Structural and functional modifications of neuronal lipid rafts: implications for HIV-associated neurological disorders.Journal of neuroinflammation · 2026Article
- Maladaptive Trained Immunity Drives Persistent IL-6 Production and Enhanced TLR Responsiveness in Monocyte-Derived Macrophages from People Living with HIV.Microorganisms · 2026Article
- HIV associated epigenetic trends and chronic diseases: insights into the hidden burden of chronic infection.Clinical epigenetics · 2026Review
- Residual HIV activity and host immunometabolic remodeling during antiretroviral therapy: implications for cardiovascular-kidney-metabolic risk.Frontiers in immunology · 2026Review
- HIV-1 Nef inhibits the JAK/STAT signaling pathway by inducing proteasomal degradation of STAT1.PloS one · 2026Article
- The prefrontal cortex as a target of HIV-1 neurotoxicity: molecular mechanisms of viral protein-mediated neurodegeneration and executive dysfunction.Frontiers in cellular neuroscience · 2026Review
- Nef as a driver of immunodeficiency and HIV-associated diseases: insights from mouse models.Frontiers in immunology · 2026Review
- Single-cell RNA sequencing analysis reveals a novel porcine alveolar macrophage subtype with high SLAMF7 expression promoting PRRSV infection.Virulence · 2025Article
- Simian Immunodeficiency Virus-Derived Extracellular Vesicles Induce a Chronic Inflammatory Phenotype in Healthy Astrocytes Unresolved by Anti-Retroviral Therapy.Pharmaceutics · 2025Article
- TREM-1 Interacts with Rotavirus Proteins and Drives Inflammatory Responses: A Combined Experimental and Computational Approach.Pathogens (Basel, Switzerland) · 2025Article
- Role of HIV-encoded proteins in cardiovascular disease.American journal of physiology. Cell physiology · 2025Review
- Increased Atherosclerosis in HIV-Infected Humanized Mice Is Caused by a Single Viral Protein, Nef.The Journal of infectious diseases · 2025Article
- HIV-1 Nef synergizes with APOL1-G1 to induce nephrocyte cell death in HIV-related kidney diseases.Disease models & mechanisms · 2025Article
- Understanding residual risk of cardiovascular disease in people with HIV.Current opinion in HIV and AIDS · 2025Review
- Immuno-cell metabolic changes in HIV-1 infection.Infectious diseases & immunity · 2025Review
39 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
HIV infection has a profound effect on "bystander" cells causing metabolic co-morbidities. This may be mediated by exosomes secreted by HIV-infected cells and containing viral factors. Here we show that exosomes containing HIV-1 protein Nef (exNef) are rapidly taken up by macrophages releasing Nef into the cell interior. This caused down-regulation of ABCA1, reduction of cholesterol efflux and sharp elevation of the abundance of lipid rafts through reduced activation of small GTPase Cdc42 and decreased actin polymerization. Changes in rafts led to re-localization of TLR4 and TREM-1 to rafts, phosphorylation of ERK1/2, activation of NLRP3 inflammasome, and increased secretion of pro-inflammatory cytokines. The effects of exNef on lipid rafts and on inflammation were reversed by overexpression of a constitutively active mutant of Cdc42. Similar effects were observed in macrophages treated with exosomes produced by HIV-infected cells or isolated from plasma of HIV-infected subjects, but not with exosomes from cells and subjects infected with ΔNef-HIV or uninfected subjects. Mice injected with exNef exhibited monocytosis, reduced ABCA1 in macrophages, increased raft abundance in monocytes and augmented inflammation. Thus, Nef-containing exosomes potentiated pro-inflammatory response by inducing changes in cholesterol metabolism and reorganizing lipid rafts. These mechanisms may contribute to HIV-associated metabolic co-morbidities.
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