Abstract
Human immunodeficiency virus type 1 (HIV) infects macrophages and microglia in the CNS and frequently causes neurocognitive impairment. Although antiviral therapy generally reduces the viral load in the CNS and improves HIV-associated neurological dysfunction, most current antiviral drugs have poor CNS penetrance and cannot completely suppress viral replication. Furthermore, drug-resistance mutations can evolve independently in the CNS. Thus, a longlived viral reservoir persists in macrophages and microglia in the brain despite antiviral therapy. This review discusses mechanisms underlying the neurotropism of HIV, focusing on the role of the HIV envelope glycoproteins and their interactions with CD4 and the chemokine receptors CCR5 and CXCR4. We review data from studies of neurotropic HIV derived from the brains of patients with HIV-associated neurocognitive impairment as well as studies of nonhuman primate models. Understanding mechanisms that underlie HIV neurotropism and neurovirulence is critical for development of therapeutics to inhibit CNS infection and preventing neurological injury in HIV-infected individuals.
Keywords: HIV, CCR5, macrophages, microglia, neurotropism
Current HIV Research
Title: Mechanisms of HIV-1 Neurotropism
Volume: 4 Issue: 3
Author(s): Rebecca Dunfee, Elaine R. Thomas, Paul R. Gorry, Jianbin Wang, Petronela Ancuta and Dana Gabuzda
Affiliation:
Keywords: HIV, CCR5, macrophages, microglia, neurotropism
Abstract: Human immunodeficiency virus type 1 (HIV) infects macrophages and microglia in the CNS and frequently causes neurocognitive impairment. Although antiviral therapy generally reduces the viral load in the CNS and improves HIV-associated neurological dysfunction, most current antiviral drugs have poor CNS penetrance and cannot completely suppress viral replication. Furthermore, drug-resistance mutations can evolve independently in the CNS. Thus, a longlived viral reservoir persists in macrophages and microglia in the brain despite antiviral therapy. This review discusses mechanisms underlying the neurotropism of HIV, focusing on the role of the HIV envelope glycoproteins and their interactions with CD4 and the chemokine receptors CCR5 and CXCR4. We review data from studies of neurotropic HIV derived from the brains of patients with HIV-associated neurocognitive impairment as well as studies of nonhuman primate models. Understanding mechanisms that underlie HIV neurotropism and neurovirulence is critical for development of therapeutics to inhibit CNS infection and preventing neurological injury in HIV-infected individuals.
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Cite this article as:
Dunfee Rebecca, Thomas R. Elaine, Gorry R. Paul, Wang Jianbin, Ancuta Petronela and Gabuzda Dana, Mechanisms of HIV-1 Neurotropism, Current HIV Research 2006; 4 (3) . https://dx.doi.org/10.2174/157016206777709500
DOI https://dx.doi.org/10.2174/157016206777709500 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
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Management of HIV: Management of HIV: old challenges and new needs
The aim of this thematic issue is to provide the most recent updates regarding the effective management of HIV infection. Antiretroviral therapy (ART) has significantly decreased HIV-related mortality, leading to an enhancement in the quality of life and life expectancy for people living with HIV (PLWH). Despite the numerous advancements ...read more
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