HIV Neuroinflammation: The Role of Exosomes in Cell Signaling, Prognostic and Diagnostic Biomarkers and Drug Delivery

Abstract

Fifty to sixty percent of HIV-1 positive patients experience HIV-1 associated neurocognitive disorders (HAND) likely due to persistent inflammation and blood–brain barrier (BBB) dysfunction. The role that microglia and astrocytes play in HAND pathogenesis has been well delineated; however, the role of exosomes in HIV neuroinflammation and neuropathogenesis is unclear. Exosomes are 50–150 nm phospholipid bilayer membrane vesicles that are responsible for cell-to-cell communication, cellular signal transduction, and cellular transport. Due to their diverse intracellular content, exosomes, are well poised to provide insight into HIV neuroinflammation as well as provide for diagnostic and predictive information that will greatly enhance the development of new therapeutic interventions for neuroinflammation. Exosomes are also uniquely positioned to be vehicles to delivery therapeutics across the BBB to modulate HIV neuroinflammation. This mini-review will briefly discuss what is known about exosome signaling in the context of HIV in the central nervous system (CNS), their potential for biomarkers as well as their potential for vehicles to deliver various therapeutics to treat HIV neuroinflammation.

The extracellular vesicles in HIV infection and progression: mechanisms, and theranostic implications

“…EVs contain a variety of host cell-derived proteins and nucleic acids, whereas HIV particles are composed of viral proteins and genetic material. EVs from HIV-infected cells can modulate the immune response, either enhancing or suppressing viral spread ( Mahajan et al, 2021 ). They can carry viral antigens, potentially impacting the body’s immune recognition and response to HIV ( Alvarez-Erviti et al, 2011 ).…”

The potential role of HIV-1 latency in promoting neuroinflammation and HIV-1-associated neurocognitive disorder

“…One compelling direct measure of neuroinflammation in HAND was the observation that antibody titers against myelin oligodendrocyte glycoprotein in the CSF were significantly higher in patients with active HAND than in asymptomatic HIV-1-infected patients [29]. Elevated concentrations of neurotoxins were also found in the brains of HIV-1-infected patients [30].…”

The multiple faces of extracellular vesicles released by microglia: Where are we 10 years after?

“…Finally, microglial EVs can also participate to HIV-1 associated neurocognitive disorders (HAND) linked to BBB dysfunction and persistent inflammation by incorporating viral proteins ( Mahajan et al, 2021 ). In fact, microglia transfected with Nef (a viral protein involved in HIV replication and a main determinant of viral pathogenesis) release Nef-carrying EVs that are able to disrupt the integrity of the BBB ( Raymond et al, 2016 ).…”