Effects of HIV gp120 on Neuroinflammation in Immunodeficient vs. Immunocompetent States

Arabatzis, Taxiarhia J; Wakley, Alexa A.; McLane, Virginia D.; Canonico, Dalton; Cao, Ling

doi:10.1007/s11481-020-09936-5

Cited by 4 publications

(2 citation statements)

References 75 publications

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“…Glycoprotein 120 also exerts indirect effects to promote neurotoxicity via the activation of monocyte-derived cells, such as microglia, the predominate reservoirs of HIV in the CNS. Soluble gp120 activates NF-κB, thereby increasing cytokines from immune cells [ 10 , 11 , 12 ]. These direct and indirect neurotoxic effects of gp120 may damage neurocircuits, impairing communication from the CNS to peripheral targets.…”

Section: Introductionmentioning

confidence: 99%

Physiological Corticosterone Attenuates gp120-Mediated Microglial Activation and Is Associated with Reduced Anxiety-Like Behavior in gp120-Expressing Mice

Moss

Mahdi

Worth

et al. 2023

Viruses

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Despite the benefits of combinatorial antiretroviral therapies (cART), virotoxic HIV proteins are still detectable within the central nervous system. Approximately half of all cART-treated patients contend with neurological impairments. The mechanisms underlying these effects likely involve virotoxic HIV proteins, including glycoprotein 120 (gp120). Glycoprotein-120 is neurotoxic due to its capacity to activate microglia. Corticosterone has been found to attenuate neuronal death caused by gp120-induced microglial cytokine production in vitro. However, the concentration-dependent effects of corticosterone on microglial activation states and the associated behavioral outcomes are unclear. Herein, we conducted parallel in vitro and in vivo studies to assess gp120-mediated effects on microglial activation, motor function, anxiety- and depression-like behavior, and corticosterone’s capacity to attenuate these effects. We found that gp120 activated microglia in vitro, and corticosterone attenuated this effect at an optimal concentration of 100 nM. Transgenic mice expressing gp120 demonstrated greater anxiety-like behavior on an elevated plus maze, and a greater duration of gp120 exposure was associated with motor deficits and anxiety-like behavior. Circulating corticosterone was lower in gp120-expressing males and diestrous females. Greater circulating corticosterone was associated with reduced anxiety-like behavior. These findings may demonstrate a capacity for glucocorticoids to attenuate gp120-mediated neuroinflammation and anxiety-like behavior.

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Section: Introductionmentioning

confidence: 99%

Physiological Corticosterone Attenuates gp120-Mediated Microglial Activation and Is Associated with Reduced Anxiety-Like Behavior in gp120-Expressing Mice

Moss

Mahdi

Worth

et al. 2023

Viruses

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“…Once inside the CNS, HIV-1 utilises various mechanisms to induce neuronal damage, thereby contributing to the development of HAND [ 2 ]. Several viral proteins are involved in HIV-1 associated neuropathogenesis, including; glycoprotein 120 (gp120) [ 3 – 5 ], transactivator of transcription (Tat) [ 6 – 8 ], negative factor (Nef) [ 9 , 10 ], regulator of expression of virion proteins (Rev) [ 11 ] and viral protein R (Vpr) [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Viral protein R (Vpr)-induced neuroinflammation and its potential contribution to neuronal dysfunction: a scoping review

Williams

Naudé

2023

BMC Infect Dis

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HIV-associated neurocognitive disorders (HAND) are the result of the activity of HIV-1 within the central nervous system (CNS). While the introduction of antiretroviral therapy (ART) has significantly reduced the occurrence of severe cases of HAND, milder cases still persist. The persistence of HAND in the modern ART era has been linked to a chronic dysregulated inflammatory profile. There is increasing evidence suggesting a potential role of Viral protein R (Vpr) in dysregulating the neuroinflammatory processes in people living with HIV (PLHIV), which may contribute to the development of HAND. Since the role of Vpr in neuroinflammatory mechanisms has not been clearly defined, we conducted a scoping review of fundamental research studies on this topic. The review aimed to assess the size and scope of available research literature on this topic and provide commentary on whether Vpr contributes to neuroinflammation, as highlighted in fundamental studies. Based on the specified selection criteria, 10 studies (6 of which were cell culture-based and 4 that included both animal and cell culture experiments) were eligible for inclusion. The main findings were that (1) Vpr can increase neuroinflammatory markers, with studies consistently reporting higher levels of TNF-α and IL-8, (2) Vpr induces (neuro)inflammation via specific pathways, including the PI3K/AKT, p38-MAPk, JNK-SAPK and Sur1-Trpm4 channels in astrocytes and the p38 and JNK-SAPK in myeloid cells, and (3) Vpr-specific protein amino acid signatures (73R, 77R and 80A) may play an important role in exacerbating neuroinflammation and the neuropathophysiology of HAND. Therefore, Vpr should be investigated for its potential contribution to neuroinflammation in the development of HAND.

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Effects of Morphine on Gp120-induced Neuroinflammation Under Immunocompetent Vs. Immunodeficient Conditions

Canonico

Casale

Look

et al. 2022

J Neuroimmune Pharmacol

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Effects of HIV gp120 on Neuroinflammation in Immunodeficient vs. Immunocompetent States

Cited by 4 publications

References 75 publications

Physiological Corticosterone Attenuates gp120-Mediated Microglial Activation and Is Associated with Reduced Anxiety-Like Behavior in gp120-Expressing Mice

Physiological Corticosterone Attenuates gp120-Mediated Microglial Activation and Is Associated with Reduced Anxiety-Like Behavior in gp120-Expressing Mice

Viral protein R (Vpr)-induced neuroinflammation and its potential contribution to neuronal dysfunction: a scoping review

Effects of Morphine on Gp120-induced Neuroinflammation Under Immunocompetent Vs. Immunodeficient Conditions

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