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.
Highlights
The lifespan of patients with HIV-1 has significantly improved due to combination therapy with highly active antiretroviral therapy (HAART)
This study suggests that cerebral spinal fluid (CSF) exosomes may be a valuable source of biomarkers (Guha et al, 2019a), which is further supported by findings from this same laboratory that a novel CSF exosome biomarker, neurofilament light chain, correlates with neurocognitive impairment in cART-treated HIVpositive individuals (Guha et al, 2019b)
This study demonstrates the role that peripheral exosomes may play in neuroinflammation or HIV-1 associated neurocognitive disorders (HAND), as amyloid beta (Aβ) production may increase the severity of HAND (Khan et al, 2016)
Summary
The lifespan of patients with HIV-1 has significantly improved due to combination therapy with highly active antiretroviral therapy (HAART). Studies have shown that HIV structural and accessory proteins Gag (Booth et al, 2006; Fang et al, 2007; Columba Cabezas and Federico, 2013) and Nef (Lenassi et al, 2010; Shelton et al, 2012; Aqil et al, 2013, 2014; Arenaccio et al, 2014a) are secreted in exosomes from various cells types. TAR RNA-exosomes significantly increases the levels of interleukin-6 (IL-6) and tumor necrosis factor-β (TNF-β) (Chen et al, 2018) These studies demonstrate the role of exosomes in modulating HIV signaling in the periphery. Combined, these studies support the potential role of exosomes for diagnostic biomarkers of HAND. These exosomes transfer Aβ to astrocytes (András et al, 2017)
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