Friends Turn Foe—Astrocytes Contribute to Neuronal Damage in NeuroAIDS

Pandey, Hriday Shanker; Seth, Pankaj

doi:10.1007/s12031-019-01357-1

Cited by 16 publications

(16 citation statements)

References 101 publications

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“…While macrophages and microglia exhibit productive infection and can release viral particles, astrocytes become infected, but they show restricted HIV-1 replication and nonproductive infection (reviewed in Churchill and Nath, 2013; Zorec et al., 2019). However, this is a double-edged sword ; on one hand, nonproductive astroglial infection reduces brain damage, which would be otherwise a devastating CNS disorder, but on the other hand, it allows for HIV-1 to latently persist in the brain parenchyma even in successfully treated patients with low viral load (reviewed in Pandey and Seth, 2019). Moreover, in patients with HIV-associated dementia, more than 19% of astrocytes have HIV sequences, and the abundance is higher in astrocytes that are in close proximity to macrophages, especially at the perivascular regions (Churchill et al., 2009; reviewed in Pandey and Seth, 2019).…”

Section: Other Human Cov That Show Neurotropismmentioning

confidence: 99%

“…However, this is a double-edged sword ; on one hand, nonproductive astroglial infection reduces brain damage, which would be otherwise a devastating CNS disorder, but on the other hand, it allows for HIV-1 to latently persist in the brain parenchyma even in successfully treated patients with low viral load (reviewed in Pandey and Seth, 2019). Moreover, in patients with HIV-associated dementia, more than 19% of astrocytes have HIV sequences, and the abundance is higher in astrocytes that are in close proximity to macrophages, especially at the perivascular regions (Churchill et al., 2009; reviewed in Pandey and Seth, 2019). In addition, it is not clear how viral persistence affects the normal homeostatic functions of astrocytes that are essential for the CNS functionality.…”

Section: Other Human Cov That Show Neurotropismmentioning

confidence: 99%

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Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

2020

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With confirmed coronavirus disease 2019 (COVID-19) cases surpassing the 18 million mark around the globe, there is an imperative need to gain comprehensive understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are associated with respiratory or intestinal symptoms, reports of neurological signs and symptoms are increasing. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the central nervous system (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood–brain barrier. Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS rennin-angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for Middle East respiratory syndrome coronavirus (MERS-CoV). Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes, and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to disbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this comprehensive review, we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV; explore the potential role for astrocytes and microglia in the infection and neuroinflammation; and compare them with the previously described human and animal CoV that showed neurotropism to propose possible underlying mechanisms.

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Section: Other Human Cov That Show Neurotropismmentioning

confidence: 99%

Section: Other Human Cov That Show Neurotropismmentioning

confidence: 99%

Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

2020

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“…After primary peripheral infection, the human immunodeficiency virus (HIV) crosses the blood-brain barrier (BBB) using monocytes as a vehicle, gaining access to the central nervous system (CNS) [1,2]. After that, the HIV infects both microglia and a small population of astrocytes [3,4], adversely affecting proper glial cell function and concomitant survival of neighboring neurons [5,6]. The latter has been linked to the release of proinflammatory cytokines and free radicals, cytoplasmic Ca 2+ imbalance and glutamate excitotoxicity [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…After that, the HIV infects both microglia and a small population of astrocytes [3,4], adversely affecting proper glial cell function and concomitant survival of neighboring neurons [5,6]. The latter has been linked to the release of proinflammatory cytokines and free radicals, cytoplasmic Ca 2+ imbalance and glutamate excitotoxicity [5,6]. In parallel, infected glial cells release soluble viral proteins into the brain parenchyma, triggering direct neuronal toxicity [7,8].…”

Section: Introductionmentioning

confidence: 99%

HIV gp120 Protein Increases the Function of Connexin 43 Hemichannels and Pannexin-1 Channels in Astrocytes: Repercussions on Astroglial Function

Gajardo-Gómez

Santibáñez

Labra

et al. 2020

IJMS

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At least half of human immunodeficiency virus (HIV)-infected individuals suffer from a wide range of cognitive, behavioral and motor deficits, collectively known as HIV-associated neurocognitive disorders (HAND). The molecular mechanisms that amplify damage within the brain of HIV-infected individuals are unknown. Recently, we described that HIV augments the opening of connexin-43 (Cx43) hemichannels in cultured human astrocytes, which result in the collapse of neuronal processes. Whether HIV soluble viral proteins such as gp120, can regulate hemichannel opening in astrocytes is still ignored. These channels communicate the cytosol with the extracellular space during pathological conditions. We found that gp120 enhances the function of both Cx43 hemichannels and pannexin-1 channels in mouse cortical astrocytes. These effects depended on the activation of IL-1β/TNF-α, p38 MAP kinase, iNOS, cytoplasmic Ca2+ and purinergic signaling. The gp120-induced channel opening resulted in alterations in Ca2+ dynamics, nitric oxide production and ATP release. Although the channel opening evoked by gp120 in astrocytes was reproduced in ex vivo brain preparations, these responses were heterogeneous depending on the CA1 region analyzed. We speculate that soluble gp120-induced activation of astroglial Cx43 hemichannels and pannexin-1 channels could be crucial for the pathogenesis of HAND.

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“…Astroglia play a signi cant role in human immunode ciency virus (HIV)-1 neuropathogenesis [6][7][8]. In fact, in the post-HAART era, the glia-mediated indirect neuronal death is prominent over the direct death of the neurons caused by the virus or the viral proteins.…”

Section: Introductionmentioning

confidence: 99%

Coronin 1A Expression in Human Astroglia, its Function in Physiology and Astrogliosis in HIV-1 Neuropathogenesis

Pandey

Kapoor

Bindu

et al. 2020

Preprint

Self Cite

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In most neurodegenerative disorders, including neuroAIDS, reactive astroglia are detrimental to the neuronal population. Calcium and its downstream regulators play a central role in mediating glial activation. Coronin 1A, an acting binding protein, majorly reported in cells of hematopoietic origin, regulates cell activity in a calcium-dependent manner, but its role in astroglial physiology and astrogliosis is largely unknown. Using a well-characterized primary culture of human astroglia and neurons, we explored the roles of Coronin 1A in astroglia physiology and the mechanisms by which it facilitates reactive astrogliosis. In this study, we report for the first time, that human primary astroglia express Coronin 1A, and it plays activity-dependent roles in events such as PLCγ1 phosphorylation followed by Calcium mobilization from the intracellular stores. HIV-1 Tat, a potent neurotoxicant that induces astrogliosis, enhances the expression of Coronin 1A, apart from affecting GFAP and pro-inflammatory molecules. Downregulation of Coronin 1A ameliorated the HIV-1 Tat-induced deleterious effects of reactive astroglia, measured as enhanced GFAP expression and release of IL-6, and Glutamate and thus reduced glia-mediated neurodegeneration. Our findings also suggest that out of a pool of dysregulated miRNAs studied by us, hsa-miR-92b-5p regulates Coronin 1A expression which further facilitates reactive astrogliosis under the effect of HIV-1 Tat. These findings highlight the novel roles of Coronin 1A in regulating the astroglial physiology and astrogliosis observed in HIV-1 neuropathogenesis.

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Friends Turn Foe—Astrocytes Contribute to Neuronal Damage in NeuroAIDS

Cited by 16 publications

References 101 publications

Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

HIV gp120 Protein Increases the Function of Connexin 43 Hemichannels and Pannexin-1 Channels in Astrocytes: Repercussions on Astroglial Function

Coronin 1A Expression in Human Astroglia, its Function in Physiology and Astrogliosis in HIV-1 Neuropathogenesis

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