Emerging Role of Nef in the Development of HIV Associated Neurological Disorders

Despite adherence to treatment, individuals living with HIV have an increased risk for developing cognitive impairments, referred to as HIV-associated neurological disorders (HAND). Due to continued growth in the HIV population, particularly amongst the aging cohort, the neurobiological mechanisms o...

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Bibliographic Details
Published in:Journal of neuroimmune pharmacology 2021-06, Vol.16 (2), p.238-250
Main Authors: Yarandi, Shadan S, Duggan, Michael R, Sariyer, Ilker K
Format: Article
Language:English
Subjects:
AIDS Dementia Complex - metabolism
AIDS Dementia Complex - virology
Animals
Autophagy
Autophagy - physiology
Extracellular vesicles
Extracellular Vesicles - metabolism
Extracellular Vesicles - virology
HIV
Human immunodeficiency virus
Humans
Models, Neurological
nef Gene Products, Human Immunodeficiency Virus - metabolism
Neurological disorders
Neurons - virology
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Summary:Despite adherence to treatment, individuals living with HIV have an increased risk for developing cognitive impairments, referred to as HIV-associated neurological disorders (HAND). Due to continued growth in the HIV population, particularly amongst the aging cohort, the neurobiological mechanisms of HAND are increasingly relevant. Similar to other viral proteins (e.g. Tat, Gp120, Vpr), the Negative Factor (Nef) is associated with numerous adverse effects in the CNS as well as cognitive impairments. In particular, emerging data indicate the consequences of Nef may be facilitated by the modulation of cellular autophagy as well as its inclusion into extracellular vesicles (EVs). The present review examines evidence for the molecular mechanisms by which Nef might contribute to neuronal dysfunction underlying HAND, with a specific focus on autophagy and EVs. Based on the these data, we propose an integrated model by which Nef may contribute to underlying neuronal dysfunction in HAND and highlight potentially novel therapeutic targets for HAND. Graphical abstract.
ISSN:1557-1890
1557-1904
DOI:10.1007/s11481-020-09964-1