HIV, NeuroAIDS, drug abuse & EVs

This paper summarizes the proceedings of a 2015 satellite symposium held by the International Society for Extracellular Vesicles (ISEV) focusing on the intersection of HIV, NeuroAIDS, drug abuse, and extracellular vesicles (EVs). While EVs were historically dismissed as cellular "junk," they are now recognized as essential nanovesicles that facilitate intercellular communication. In the context of HIV and neuroinflammatory disease, EVs are emerging as key players in transmitting pathological signals between cells, potentially contributing to the persistence of cognitive impairment despite successful antiretroviral therapy.

The symposium highlighted several distinct pathways through which EVs propagate disease:

• Cytokine Transport: Research presented suggests that cytokines in HIV-infected patients are not free-floating but are instead selectively enriched within EVs, allowing them to activate distant immune cells.
• Neuroinflammation: Astrocyte-derived EVs can transport specific microRNAs (such as miR-9) to microglia, directly inducing inflammatory states and cell migration within the central nervous system (CNS).
• Peripheral-Brain Crosstalk: Evidence indicates that EVs shed by astrocytes in response to brain injury can cross the blood-brain barrier and signal to the liver, modulating the systemic inflammatory response via PPAR signaling pathways.
• Viral Mimicry: HIV-infected cells produce EVs containing TAR RNA, which can be taken up by uninfected cells, activating proinflammatory pathways (such as NF-κB) and potentially contributing to cellular exhaustion and death.

Understanding the role of EVs provides a novel lens through which to view HIV-associated neurological disorders (HAND). Because current antiretroviral therapies often fail to fully resolve cognitive deficits, identifying these EV-mediated mechanisms offers potential targets for diagnostic biomarkers or therapeutic interventions. The ability to manipulate EV cargo or inhibit specific signaling pathways could help mitigate chronic inflammation and neurodegeneration associated with HIV infection.