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Chemokine Receptors and NeuroAIDS pp 5–31Cite as

HIV Neuroinvasion: Early Events, Late Manifestations

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Abstract

Human immunodeficiency virus type 1 (HIV-1) infection affects more that 32 million people worldwide (2007) and is associated with central nervous system (CNS) dysfunction in at least 30% of infected individuals, despite treatment with highly active antiretroviral therapy (HAART). The spectrum of cognitive disorders ranges from mild impairment of higher cortical functions to dementia (HIV associated dementia, HAD) and HIV-associated neurocognitive disorders (HAND). The use of HAART has lessened the severity but not the prevalence of HAND, and improving neurological outcomes will require more effective antiviral drug effects in the CNS and adjunctive therapies directed toward mechanisms and pathways of HIV-induced neurodegeneration. Identifying such targets requires understanding the events preceding irreversible neuronal damage in the CNS: HIV entry, replication in cellular reservoirs, neuroimmune activation, production of neurotoxins (HIV proteins and cellular factors), and neuronal repair responses. Studies of HIV infected individuals and simian immunodeficiency virus (SIV)–infected macaques, and numerous in vitro model systems of HIV neurodegeneration have suggested a central role for chemokines and their receptors in modulating these pathogenic processes during the course of CNS infection. This chapter addresses selected aspects of our current understanding of HIV neuropathogenesis, based on in vivo and in vitro studies, which are modulated directly and indirectly through chemokine/chemokine receptor interactions. Some of these associations are firmly established through published studies, and others are more speculative. Without doubt, many of the steps in HIV neuropathogenesis apply to other neurodegenerative diseases, and common approaches for neuroprotection will most likely emerge.

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Authors and Affiliations

  1. Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Maria F. Chen, Samantha Soldan & Dennis L. Kolson

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  1. Maria F. Chen
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  2. Samantha Soldan
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  3. Dennis L. Kolson
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Correspondence to Dennis L. Kolson .

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  1. Dept. Pharmacology & Physiology, & Institute of Molecular Medicine, Drexel University College of Medicine, North 15th St. 245, Philadelphia, 19102-1101, USA

    Olimpia Meucci

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Chen, M.F., Soldan, S., Kolson, D.L. (2010). HIV Neuroinvasion: Early Events, Late Manifestations. In: Meucci, O. (eds) Chemokine Receptors and NeuroAIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0793-6_2

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