Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: implications for HIV-1 infection

Journal of Neuroinflammation, Год журнала: 2021, Номер 18(1)

Опубликована: Июль 29, 2021

Abstract Background Neurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 infect brains. While mechanisms this process not fully understood, it has been proposed that can cells neurovascular unit (NVU), which form blood-brain barrier (BBB). The aim current study was analyze expression pattern main receptors naïve and HIV-1-infected NVU order elucidate a possible pathway virus entry into brain potential modulatory impact HIV-1 process. Methods gene protein profile ACE2, TMPRSS2, ADAM17, BSG, DPP4, AGTR2, ANPEP, cathepsin B, L assessed qPCR, immunoblotting, immunostaining, respectively. In addition, we investigated if endothelial be exposure S1 subunit S protein, domain responsible for direct binding ACE2 receptors. Results involved infection co-expressed NVU, especially astrocytes microglial cells. These functionally active as SARS CoV-2 altered tight junction proteins, such claudin-5 ZO-1. Additionally, upregulated TMPRSS2 microglia Conclusions findings provide key insight recognition may help develop treatment CNS COVID-19.

Язык: Английский

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HIV in the Brain: Identifying Viral Reservoirs and Addressing the Challenges of an HIV Cure

Vaccines, Год журнала: 2021, Номер 9(8), С. 867 - 867

Опубликована: Авг. 5, 2021

Advances in antiretroviral therapy have prolonged the life of people living with HIV and diminished level virus these individuals. Yet, quickly rebounds after disruption and/or cessation treatment due to significant cellular anatomical reservoirs for HIV, which underscores challenge cure strategies. The central nervous system (CNS), particular, is seeded within 1–2 weeks infection a reservoir HIV. In this review, we address paradigm CNS relevant cell types, including astrocytes microglia, that been shown harbor viral even treatment. focus on developmental aspects microglia lead their susceptibility infection, how propagates among cells. We also challenges measuring latent reservoir, advances detection assays, curative strategies evolved regard reservoir. Current still require optimization reduce or eliminate may contribute levels neuroinflammation cognitive decline. With mind, brain should remain prominent when assessing options overall burden clinic, especially context HIV-associated neurocognitive disorders (HAND).

Язык: Английский

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The Causes and Long-Term Consequences of Viral Encephalitis

Frontiers in Cellular Neuroscience, Год журнала: 2021, Номер 15

Опубликована: Ноя. 30, 2021

Reports regarding brain inflammation, known as encephalitis, have shown an increasing frequency during the past years. Encephalitis is a relevant concern to public health due its high morbidity and mortality. Infectious or autoimmune diseases are most common cause of encephalitis. The clinical symptoms this pathology can vary depending on zone affected, with mild ones such fever, headache, confusion, stiff neck, severe ones, seizures, weakness, hallucinations, coma, among others. affect individuals all ages, but it frequently observed in pediatric elderly populations, causes viral infections. Several agents been described induce arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumovirus, coronaviruses, Once neurotropic virus reaches parenchyma, resident cells neurons, astrocytes, microglia, be infected, promoting secretion pro-inflammatory molecules subsequent immune cell infiltration that leads damage. After resolving infection, local response remain active, contributing long-term neuropsychiatric disorders, neurocognitive impairment, degenerative diseases. In article, we will discuss how viruses reach brain, impact encephalitis function, focus especially sequelae reported even after clearance.

Язык: Английский

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Innate Immune Sensing of Viruses and Its Consequences for the Central Nervous System

Viruses, Год журнала: 2021, Номер 13(2), С. 170 - 170

Опубликована: Янв. 23, 2021

Viral infections remain a global public health concern and cause severe societal economic burden. At the organismal level, innate immune system is essential for detection of viruses constitutes first line defense. components are sensed by host pattern recognition receptors (PRRs). PRRs can be further classified based on their localization into Toll-like (TLRs), C-type lectin (CLR), retinoic acid-inducible gene-I (RIG-I)-like (RLRs), NOD-like (NLRs) cytosolic DNA sensors (CDS). TLR RLR signaling results in production type I interferons (IFNα -β) pro-inflammatory cytokines cell-specific manner, whereas NLR leads to interleukin-1 family proteins. On other hand, CLRs capable sensing glycans present viral pathogens, which induce phagocytic, endocytic, antimicrobial, pro- inflammatory responses. Peripheral ensuing cytokine response significantly affect central nervous (CNS). But also directly enter CNS via multitude routes, such as nasal epithelium, along nerve fibers connecting periphery cargo infiltrating infected cells passing through blood brain barrier, triggering responses CNS. Here, we review mechanisms currently recognized consequences viruses.

Язык: Английский

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Single-Cell RNA-Sequencing: Astrocyte and Microglial Heterogeneity in Health and Disease

Cells, Год журнала: 2022, Номер 11(13), С. 2021 - 2021

Опубликована: Июнь 24, 2022

Astrocytes and microglia are non-neuronal cells that maintain homeostasis within the central nervous system via their capacity to regulate neuronal transmission prune synapses. Both astrocytes can undergo morphological transcriptomic changes in response infection with human immunodeficiency virus (HIV). While both be infected HIV, HIV viral proteins local environment interact activate these cells. Given play critical roles maintaining function, it will have an understanding of heterogeneity identify genes mechanisms modulate responses HIV. Heterogeneity may include a depletion or increase one more astrocyte microglial subtypes different regions brain spine as well gain loss specific function. Single-cell RNA sequencing (scRNA-seq) has emerged powerful tool used characterise given population. The use this method facilitates identification cellular transcriptomes develop activation various disease processes. In review, we examine recent studies scRNA-seq explore neurodegenerative diseases including Alzheimer’s amyotrophic lateral sclerosis infection. A careful review expand our current at states.

Язык: Английский

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Neuroinflammation in HIV-associated depression: evidence and future perspectives

Molecular Psychiatry, Год журнала: 2022, Номер 27(9), С. 3619 - 3632

Опубликована: Май 26, 2022

Abstract People living with HIV face a high risk of mental illness, especially depression. We do not yet know the precise neurobiological mechanisms underlying HIV-associated Depression severity in general population has been linked to acute and chronic markers systemic inflammation. Given associations between depression peripheral inflammation, since infection brain elicits neuroinflammatory response, it is possible that neuroinflammation contributes prevalence amongst people HIV. The purpose this review was synthesise existing evidence for depression, While there strong independent these three conditions, few preclinical or clinical studies have attempted characterise their interrelationship, representing major gap literature. This identifies key areas debate field offers perspectives future investigations pathophysiology Reproducing findings across diverse populations will be crucial obtaining robust generalisable results elucidate role pathophysiology.

Язык: Английский

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Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain

Cells, Год журнала: 2022, Номер 11(15), С. 2379 - 2379

Опубликована: Авг. 2, 2022

The major barrier to cure HIV infection is the early generation and extended survival of reservoirs in circulation tissues. Currently, techniques used detect quantify are mostly based on blood-based assays; however, it has become evident that viral remain Our study describes a novel multi-component imaging method (HIV DNA, mRNA, proteins same assay) identify, quantify, characterize tissues blood products obtained from HIV-infected individuals even when systemic replication undetectable. In human brains under ART, we identified microglia/macrophages small population astrocytes main cells with integrated DNA. Only half DNA expressed one-third proteins. Surprisingly, residual HIV-p24, gp120, nef, vpr, tat protein expression accumulation uninfected around suggesting local synthesis, secretion, bystander uptake. conclusion, our data show ART reduces size brain’s reservoirs; local/chronic secretion still occurs, indicating brain anatomical target infection.

Язык: Английский

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Involvement of lncRNA TUG1 in HIV-1 Tat-Induced Astrocyte Senescence

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4330 - 4330

Опубликована: Фев. 22, 2023

HIV-1 infection in the era of combined antiretroviral therapy has been associated with premature aging. Among various features neurocognitive disorders, astrocyte senescence surmised as a potential cause contributing to HIV-1-induced brain aging and impairments. Recently, lncRNAs have also implicated play essential roles onset cellular senescence. Herein, using human primary astrocytes (HPAs), we investigated role lncRNA TUG1 Tat-mediated We found that HPAs exposed Tat resulted significant upregulation expression was accompanied by elevated p16 p21, respectively. Additionally, Tat-exposed demonstrated increased senescence-associated (SA) markers—SA-β-galactosidase (SA-β-gal) activity SA-heterochromatin foci—cell-cycle arrest, production reactive oxygen species proinflammatory cytokines. Intriguingly, gene silencing reversed Tat-induced p16, SA-β gal activity, activation, Furthermore, astrocytic TUG1, cytokines were observed prefrontal cortices transgenic rats, thereby suggesting occurrence activation vivo. Overall, our data indicate involves could serve therapeutic target for dampening accelerated HIV-1/HIV-1 proteins.

Язык: Английский

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Ionic Liquid Coating‐Driven Nanoparticle Delivery to the Brain: Applications for NeuroHIV

Advanced Science, Год журнала: 2024, Номер 11(23)

Опубликована: Апрель 4, 2024

Abstract Delivering cargo to the central nervous system (CNS) remains a pharmacological challenge. For infectious diseases such as HIV, CNS acts latent reservoir that is inadequately managed by systemic antiretrovirals (ARTs). ARTs thus cannot eradicate and given infection, patients experience neurological deficits collectively referred “neuroHIV”. Herein, development of bioinspired ionic liquid‐coated nanoparticles (IL‐NPs) for in situ hitchhiking on red blood cells (RBCs) reported, which enables 48% brain delivery intracarotid arterial‐ infused cargo. Moreover, IL choline trans‐2‐hexenoate (CA2HA 1:2) demonstrates preferential accumulation parenchymal microglia over endothelial post‐delivery. This study further successful loading abacavir (ABC), an ART challenging encapsulate, into IL‐NPs, verifies retention antiviral efficacy vitro. IL‐NPs are not cytotoxic primary human peripheral mononuclear (PBMCs) CA2HA 1:2 coating itself confers notable anti‐viremic capacity. In addition, vitro cell culture assays show markedly increased uptake neural compared bare PLGA nanoparticles. work debuts liquids promising nanoparticle coatings assist biodistribution has potential revolutionize cargos (i.e., drugs, viral vectors) through compartmental barriers blood‐brain‐barrier (BBB).

Язык: Английский

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HIV-1 Latency and Viral Reservoirs: Existing Reversal Approaches and Potential Technologies, Targets, and Pathways Involved in HIV Latency Studies

Cells, Год журнала: 2021, Номер 10(2), С. 475 - 475

Опубликована: Фев. 23, 2021

Eradication of latent human immunodeficiency virus (HIV) infection is a global health challenge. Reactivation HIV latency and killing virus-infected cells, the so-called “kick kill” or “shock approaches, are popular strategy for cure. While antiretroviral therapy (ART) halts replication by targeting multiple steps in life cycle, including viral entry, integration, replication, production, it cannot get rid occult provirus incorporated into host-cell genome. These proviruses replication-competent can rebound cases ART interruption cessation. In general, very small population cells harbor provirus, serve as reservoirs ART-controlled subjects, capable expressing little to no RNA proteins. Beyond canonical resting memory CD4+ T also exist within tissue macrophages, myeloid brain microglial gut epithelial hematopoietic stem (HSCs). Despite lack active latently HIV-infected subjects continue exhibit aberrant cellular signaling metabolic dysfunction, leading minor major systemic complications comorbidities. include genomic DNA damage; telomere attrition; mitochondrial dysfunction; premature aging; lymphocytic, cardiac, renal, hepatic, pulmonary dysfunctions. Therefore, arcane machineries involved its reversal warrant further studies identify cryptic mechanisms reservoir formation clearance. this review, we discuss several molecules pathways, some which have dual roles maintaining reversing reservoirs, describe evolving strategies possible approaches eliminate and, ultimately, cure/eradicate infection.

Язык: Английский

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