HIV-1 Nef is carried on the surface of extracellular vesicles.

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.

Extracellular vesicles produced by HIV-1 Nef-expressing cells induce myelin impairment and oligodendrocyte damage in the mouse central nervous system.

HIV-associated neurocognitive disorders (HAND) are a spectrum of cognitive impairments that continue to affect approximately half of all HIV-positive individuals despite effective viral suppression through antiretroviral therapy (ART). White matter pathologies have persisted in the ART era, and the degree of white matter damage correlates with the degree of neurocognitive impairment in patients with HAND. The HIV protein Nef has been implicated in HAND pathogenesis, but its effect on white matter damage has not been well characterized.

Abundance of Nef and p-Tau217 in Brains of Individuals Diagnosed with HIV-Associated Neurocognitive Disorders Correlate with Disease Severance.

HIV-associated neurocognitive disorders (HAND) is a term used to describe a variety of neurological impairments observed in HIV-infected individuals. The pathogenic mechanisms of HAND and of its connection to HIV infection remain unknown, but one of the considered hypotheses suggests that HIV infection accelerates the development of Alzheimer's disease. Previous studies suggested that HIV-1 Nef may contribute to HAND by inhibiting cholesterol efflux, increasing the abundance of lipid rafts, and affecting their functionality.