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

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: July 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.

Language: Английский

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

Vaccines, Journal Year: 2021, Volume and Issue: 9(8), P. 867 - 867

Published: Aug. 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).

Language: Английский

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The Causes and Long-Term Consequences of Viral Encephalitis

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Nov. 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.

Language: Английский

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

Viruses, Journal Year: 2021, Volume and Issue: 13(2), P. 170 - 170

Published: Jan. 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.

Language: Английский

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Neuroinflammation in HIV-associated depression: evidence and future perspectives

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(9), P. 3619 - 3632

Published: May 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.

Language: Английский

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

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2379 - 2379

Published: Aug. 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.

Language: Английский

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

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: April 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).

Language: 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, Journal Year: 2021, Volume and Issue: 10(2), P. 475 - 475

Published: Feb. 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.

Language: Английский

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Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection

Viruses, Journal Year: 2021, Volume and Issue: 13(12), P. 2512 - 2512

Published: Dec. 14, 2021

Antiretroviral therapy (ART) effectively reduces cycles of viral replication but does not target proviral populations in cells that persist for prolonged periods and can undergo clonal expansion. Consequently, chronic human immunodeficiency virus (HIV) infection is sustained during ART by a reservoir long-lived latently infected their progeny. This landscape undergoes change over time on ART. One the forces driving expansion CD4 T cells, which presents key obstacle to HIV eradication. Potential mechanisms include general immune activation, antigenic stimulation, homeostatic proliferation, provirus-driven expansion, each likely contributes varying, largely unmeasured, amounts maintaining reservoir. The role clinical events, such as infections or neoplasms, these remains uncertain, characterizing may shed light approaches eradicate HIV. A limited number individuals have been cured setting bone marrow transplant; information from other studies identify means control without In this review, we describe HIV-1 persistence along with attempts modify factors part reduction cure strategies.

Language: Английский

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Biotypes of Central Nervous System Complications in People With Human Immunodeficiency Virus: Virology, Immunology, and Neuropathology

The Journal of Infectious Diseases, Journal Year: 2023, Volume and Issue: 227(Supplement_1), P. S3 - S15

Published: March 15, 2023

Abstract Despite viral suppression with antiretroviral therapy (ART), people human immunodeficiency virus (HIV) continue to experience central nervous system (CNS) complications, primarily in the form of mild cognitive impairment and mental health disorders (eg, depression, anxiety, other neuropsychiatric problems). The multifactorial pathogenesis heterogeneity mechanisms likely underlying CNS complications must be addressed development preventive interventions effective treatments. biotyping approach has previously been useful define phenotypes diseases based on could translated field neuroHIV. purpose Biotype Workshop series, Virology, Immunology Neuropathology Working Group particular, is capitalize current new technologies guide future research efforts using wealth available immunological, virologic, neuropathological data collected from HIV off ART.

Language: Английский

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