HIV‐1 Nef is carried on the surface of extracellular vesicles
Year: 2024
Type: article
Abstract: Extracellular vesicles (EVs) serve as pivotal mediators of intercellular communication in both health and disease, delivering biologically active molecules from vesicle-producing cells to recipient cells. In the context of HIV infection, EVs have been shown to carry the viral protein Nef, a key pathogenic factor associated with HIV-related co-morbidities. Despite this recognition, the specific localisation of Nef within the vesicles has remained elusive. This study addresses this critical knowledge gap by investigating Nef-containing EVs. Less than 1% of the total released Nef was associated with EVs; most Nef existed as free protein released by damaged cells. Nevertheless, activity of EV-associated Nef in downregulating the major cholesterol transporter ABCA1, a critical aspect linked to the pathogenic effects of Nef, was comparable to that of free Nef present in the supernatant. Through a series of biochemical and microscopic assays, we demonstrate that the majority of EV-associated Nef molecules are localised on the external surface of the vesicles. This distinctive distribution prompts the consideration of Nef-containing EVs as potential targets for immunotherapeutic interventions aimed at preventing or treating HIV-associated co-morbidities. In conclusion, our results shed light on the localisation and functional activity of Nef within EVs, providing valuable insights for the development of targeted immunotherapies to mitigate the impact of HIV-associated co-morbidities.
DOI: 10.1002/jev2.12478
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,410
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Lipid raft therapy – a novel therapeutic approach for HIV-associated cardiometabolic co-morbidities, Trained immunity induced by Nef-containing extracellular vesicles, District of Columbia Center for AIDS Research, Phase II study to evaluate the efficacy and safety of baricitinib for reduction of HIV in the central nervous system, Novel pathogenic mechanism of HIV-associated CNS neurological disorders, Towards high-resolution structural biology of membrane protein complexes in their native lipid environment
OpenAlex ID: W4400737651