Astrocytes are HIV reservoirs in the brain: A cell type with poor HIV infectivity and replication but efficient cell‐to‐cell viral transfer

Valdebenito, Silvana; Castellano, Paul; Ajasin, David; Eugenin, Eliseo A.

doi:10.1111/jnc.15336

Cited by 56 publications

(65 citation statements)

References 97 publications

(180 reference statements)

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“…For example, Chlamydia pneumoniae , obligate intracellular bacteria, are frequently found in microglia and astrocytes in the brain of AD patients ( Balin et al, 1998 ; Nazareth et al, 2021 ). Microglia and astrocytes are also the target of some viruses, such as CMV ( Cheeran et al, 2001 ) and HIV ( Avalos et al, 2017 ; Valdebenito et al, 2021 ). In addition, T. gondii , a neurotropic protozoan parasite causing a lifelong CNS infection, has been implicated in various neurological disorders, including dementia ( Nayeri Chegeni et al, 2019 ).…”

Section: Metabolic Disturbance and Cognitive Impairmentmentioning

confidence: 99%

Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia

Shinjyo

Kita

2021

Front. Cell. Neurosci.

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Metabolic syndromes are frequently associated with dementia, suggesting that the dysregulation of energy metabolism can increase the risk of neurodegeneration and cognitive impairment. In addition, growing evidence suggests the link between infections and brain disorders, including Alzheimer’s disease. The immune system and energy metabolism are in an intricate relationship. Infection triggers immune responses, which are accompanied by imbalance in cellular and organismal energy metabolism, while metabolic disorders can lead to immune dysregulation and higher infection susceptibility. In the brain, the activities of brain-resident immune cells, including microglia, are associated with their metabolic signatures, which may be affected by central nervous system (CNS) infection. Conversely, metabolic dysregulation can compromise innate immunity in the brain, leading to enhanced CNS infection susceptibility. Thus, infection and metabolic imbalance can be intertwined to each other in the etiology of brain disorders, including dementia. Insulin and leptin play pivotal roles in the regulation of immunometabolism in the CNS and periphery, and dysfunction of these signaling pathways are associated with cognitive impairment. Meanwhile, infectious complications are often comorbid with diabetes and obesity, which are characterized by insulin resistance and leptin signaling deficiency. Examples include human immunodeficiency virus (HIV) infection and periodontal disease caused by an oral pathogen Porphyromonas gingivalis. This review explores potential interactions between infectious agents and insulin and leptin signaling pathways, and discuss possible mechanisms underlying the relationship between infection, metabolic dysregulation, and brain disorders, particularly focusing on the roles of insulin and leptin.

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Section: Metabolic Disturbance and Cognitive Impairmentmentioning

confidence: 99%

Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia

Shinjyo

Kita

2021

Front. Cell. Neurosci.

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“…However, most treatment guidelines do not have special considerations regarding CNS HIV. Considering that the brain is one of the reservoirs of the virus, clearance of HIV from these reservoirs could lead to a cure for CNS HIV [ 13 , 15 ].…”

Section: Drug Permeation Challenges In Cns Tb Treatmentmentioning

confidence: 99%

“…Alternatively, HIV can enter the CNS through lymphocytes which retain viruses that replicate in macrophages or as free virions where the mode of entry is through endothelial cells [ 10 , 12 ]. In the brain, HIV-1 resides in the perivascular macrophages, microglial cells and astrocytes [ 13 , 14 , 15 ]. Microglial cells are the main reservoirs of HIV-1 in the CNS [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Permeation Challenges of Drugs for Treatment of Neurological Tuberculosis and HIV and the Application of Magneto-Electric Nanoparticle Drug Delivery Systems

et al. 2021

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The anatomical structure of the brain at the blood–brain barrier (BBB) creates a limitation for the movement of drugs into the central nervous system (CNS). Drug delivery facilitated by magneto-electric nanoparticles (MENs) is a relatively new non-invasive approach for the delivery of drugs into the CNS. These nanoparticles (NPs) can create localized transient changes in the permeability of the cells of the BBB by inducing electroporation. MENs can be applied to deliver antiretrovirals and antibiotics towards the treatment of human immunodeficiency virus (HIV) and tuberculosis (TB) infections in the CNS. This review focuses on the drug permeation challenges and reviews the application of MENs for drug delivery for these diseases. We conclude that MENs are promising systems for effective CNS drug delivery and treatment for these diseases, however, further pre-clinical and clinical studies are required to achieve translation of this approach to the clinic.

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“…Within days of infection, human immunodeficiency virus type 1 (HIV-1) rapidly disseminates to draining lymph nodes. HIV-1 advances to destroy helper T cells and establish latent HIV-1 reservoirs through the irreversible integration of replication-competent proviral DNA into the genome of resting CD4 + T cells, hematopoietic stem cells, cells from the monocyte-macrophage lineage, and microglia [ 1 , 2 , 3 , 4 , 5 ]. Although antiretroviral therapy (ART) has transformed HIV-1 infection from a lethal and destructive disease into a controllable, but chronic condition, the establishment of HIV-1 latency is unaffected by early initiation of ART [ 6 ], and there is no evidence that ART alone is able to eradicate latent HIV-1 [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Induction of Autophagy to Achieve a Human Immunodeficiency Virus Type 1 Cure

Campbell

Spector

2021

Cells

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Effective antiretroviral therapy has led to significant human immunodeficiency virus type 1 (HIV-1) suppression and improvement in immune function. However, the persistence of integrated proviral DNA in latently infected reservoir cells, which drive viral rebound post-interruption of antiretroviral therapy, remains the major roadblock to a cure. Therefore, the targeted elimination or permanent silencing of this latently infected reservoir is a major focus of HIV-1 research. The most studied approach in the development of a cure is the activation of HIV-1 expression to expose latently infected cells for immune clearance while inducing HIV-1 cytotoxicity—the “kick and kill” approach. However, the complex and highly heterogeneous nature of the latent reservoir, combined with the failure of clinical trials to reduce the reservoir size casts doubt on the feasibility of this approach. This concern that total elimination of HIV-1 from the body may not be possible has led to increased emphasis on a “functional cure” where the virus remains but is unable to reactivate which presents the challenge of permanently silencing transcription of HIV-1 for prolonged drug-free remission—a “block and lock” approach. In this review, we discuss the interaction of HIV-1 and autophagy, and the exploitation of autophagy to kill selectively HIV-1 latently infected cells as part of a cure strategy. The cure strategy proposed has the advantage of significantly decreasing the size of the HIV-1 reservoir that can contribute to a functional cure and when optimised has the potential to eradicate completely HIV-1.

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Astrocytes are HIV reservoirs in the brain: A cell type with poor HIV infectivity and replication but efficient cell‐to‐cell viral transfer

Cited by 56 publications

References 97 publications

Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia

Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia

Permeation Challenges of Drugs for Treatment of Neurological Tuberculosis and HIV and the Application of Magneto-Electric Nanoparticle Drug Delivery Systems

Induction of Autophagy to Achieve a Human Immunodeficiency Virus Type 1 Cure

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