HIV-1 Tat: Role in Bystander Toxicity

Frontiers in Cellular and Infection Microbiology, Journal Year: 2020, Volume and Issue: 10

Published: Feb. 25, 2020

HIV Tat protein is a critical that plays multiple roles in pathogenesis. While its role as the transactivator of transcription well-established, other non-viral replication-associated functions have been described several HIV-comorbidities even current antiretroviral therapy (ART) era. produced and released into extracellular space from cells with active replication or latently HIV-infected neighboring uninfected absence viral production due to effective ART. Neighboring can take up resulting upregulation inflammatory genes activation pathways leads cytotoxicity observed comorbidities such associated neurocognitive disorder (HAND), cardiovascular impairment, accelerated aging. Thus, understanding how modulates host response important designing novel therapeutic approaches target chronic effects soluble proteins infection.

Language: Английский

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The Influence of Virus Infection on Microglia and Accelerated Brain Aging

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1836 - 1836

Published: July 20, 2021

Microglia are the resident immune cells of central nervous system contributing substantially to health and disease. There is increasing evidence that inflammatory microglia may induce or accelerate brain aging, by interfering with physiological repair remodeling processes. Many viral infections affect interfere functions, including human deficiency virus, flaviviruses, SARS-CoV-2, influenza, herpes viruses. Especially chronic causing low-grade neuroinflammation contribute aging. This review elucidates potential role various neurotropic viruses in microglia-driven neurocognitive deficiencies possibly accelerated

Language: Английский

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HIV-1 Tat induced microglial EVs leads to neuronal synaptodendritic injury: microglia-neuron cross-talk in NeuroHIV

Extracellular Vesicles and Circulating Nucleic Acids, Journal Year: 2022, Volume and Issue: 3(2), P. 133 - 49

Published: Jan. 1, 2022

Aim: Activation of microglial NLRP3 inflammasome is an essential contributor to neuroinflammation underlying HIV-associated neurological disorders (HAND). Under pathological conditions, microglia-derived-EVs (MDEVs) can affect neuronal functions by delivering neurotoxic mediators recipient cells. However, the role in mediating synaptodendritic injury has remained unexplored date. In present study, we sought assess regulatory HIV-1 Tat induced injury. We hypothesized that mediated microglia EVs carrying significant levels contribute injury, thereby affecting maturation neurons. Methods: To understand cross-talk between and neuron, isolated from BV2 human primary (HPM) cells with or without depletion using siNLRP3 RNA. were differential centrifugation, characterized ZetaView nanoparticle tracking analysis, electron microscopy, western blot analysis for exosome markers. Purified exposed rat neurons E18 rats. Along green fluorescent protein (GFP) plasmid transfection, immunocytochemistry was performed visualize Western blotting employed measure siRNA transfection efficiency extent synaptodegeneration. Images captured confocal subsequently, Sholl analyzing dendritic spines reconstruction software Neurolucida 360. Electrophysiology on hippocampal functional assessment. Results: Our findings demonstrated expression IL1β, further these packaged exosomes (MDEV) also taken up Exposure Tat-MDEVs resulted downregulation synaptic proteins- PSD95, synaptophysin, excitatory vGLUT1, as well upregulation inhibitory Gephyrin, GAD65, implicating impaired transmissibility. showed not only caused loss but affected numbers spine sub-types- mushroom stubby. Synaptodendritic impairment evidenced decrease miniature postsynaptic currents (mEPSCs). this process, silenced microglia. exerted a protective proteins, density mEPSCs. Conclusion: summary, our study underscores important Tat-MDEV While inflammation well-described, its EV-mediated damage interesting finding, it target therapeutics HAND.

Language: Английский

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Current drugs for HIV-1: from challenges to potential in HIV/AIDS

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 26, 2023

The human immunodeficiency virus (HIV) persists in latently infected CD4 + T cells and integrates with the host genome until cell death. Acquired syndrome (AIDS) is associated HIV-1. Possibly, treating HIV/AIDS an essential but challenging clinical goal. This review provides a detailed account of types mechanisms monotherapy combination therapy against HIV-1 describes nanoparticle hydrogel delivery systems. In particular, recently developed capsid inhibitor (Lenacapavir) Ainuovirine/tenofovir disoproxil fumarate/lamivudine (ACC008) are described. It interestingly to note that lack multipass transmembrane proteins serine incorporator 3 (SERINC3) 5 (SERINC5) may be one reasons for enhanced infectivity discovery SERINC3 SERINC5 new ideas medication development. Therefore, we believe AIDS, antiviral medications should rationally selected pre-exposure post-exposure prophylaxis avoid emergence drug resistance. Attention paid research development drugs predict HIV mutations as accurately possible develop immune antibodies provide multiple guarantees cure AIDS.

Language: Английский

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Cognitive impairment in people living with HIV: mechanisms, controversies, and future perspectives

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(11), P. 1076 - 1089

Published: July 1, 2024

Language: Английский

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Animal models for studies of HIV-1 brain reservoirs

Journal of Leukocyte Biology, Journal Year: 2022, Volume and Issue: 112(5), P. 1285 - 1295

Published: Aug. 31, 2022

Abstract The HIV-1 often evades a robust antiretroviral-mediated immune response, leading to persistent infection within anatomically privileged sites including the CNS. Continuous low-level occurs in presence of effective antiretroviral therapy (ART) CD4+ T cells and mononuclear phagocytes (MP; monocytes, macrophages, microglia, dendritic cells). Within CNS, productive viral is found exclusively microglia meningeal, perivascular, choroidal macrophages. MPs serve as principal CNS reservoir. Animal models have been developed recapitulate natural human infection. These include nonhuman primates, humanized mice, EcoHIV, transgenic rodent models. used study disease pathobiology, modulatory agents, reservoirs, eradication strategies. However, each these are limited specific component(s) disease. Indeed, species specificity must drive therapeutic cure studies. studied several model systems reflective latent infections, specifically MP (myeloid, monocyte, histiocyte cell) populations. Therefore, additional small animal that allow replication enable carriage into brain virus-susceptible needed. To this end, review serves outline currently available myeloid reservoirs highlight areas lacking require future research more effectively disease-specific events could be useful for studies both outside

Language: Английский

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Shock and kill within the CNS: A promising HIV eradication approach?

Journal of Leukocyte Biology, Journal Year: 2022, Volume and Issue: 112(5), P. 1297 - 1315

Published: Sept. 23, 2022

Abstract The most studied HIV eradication approach is the “shock and kill” strategy, which aims to reactivate latent reservoir by latency reversing agents (LRAs) allowing elimination of these cells immune-mediated clearance or viral cytopathic effects. CNS an anatomic compartment in (persistent) plays important role HIV-associated neurocognitive disorder. Restriction blood–brain barrier for maintenance homeostasis microenvironment, includes CNS-specific cell types, expression transcription factors, altered immune surveillance. Within predominantly myeloid such as microglia perivascular macrophages are thought be a persistent infection. Nevertheless, infection T astrocytes might also impact CNS. Genetic adaptation this microenvironment results genetically distinct, compartmentalized populations with differences profiles. Because profiles, LRAs have different effects within compared periphery. Moreover, reactivation brain complex could detrimental consequences. Finally, independent activity on HIV, themselves can adverse neurologic We provide extensive overview current knowledge strategy. Subsequently, we reflect promise strategy

Language: Английский

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Rapid and visual identification of HIV-1 using reverse transcription loop-mediated isothermal amplification integrated with a gold nanoparticle-based lateral flow assay platform

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 12, 2023

Human immunodeficiency virus type one (HIV-1) infection remains a major public health problem worldwide. Early diagnosis of HIV-1 is crucial to treat and control this effectively. Here, for the first time, we reported novel molecular diagnostic assay called reverse transcription loop-mediated isothermal amplification combined with visual gold nanoparticle-based lateral flow (RT-LAMP-AuNPs-LFA), which devised rapid, specific, sensitive, identification HIV-1. The unique LAMP primers were successfully designed based on pol gene from genotypes CRF01_AE, CRF07_BC, CRF08_BC, subtype B, are prevalent in China. optimal HIV-1-RT-LAMP-AuNPs-LFA reaction conditions determined be 68°C 35 min. detection procedure, including crude genomic RNA isolation (approximately 5 min), RT-LAMP (35 result readout (<2 can completed within 45 Our has limit 20 copies per test, did not observe any cross-reactivity other pathogen our testing. Hence, preliminary results indicated that potentially serve as useful point-of-care tool clinical setting.

Language: Английский

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PKR Inhibitor C16 Regulates HIV-gp120 Induced Neuronal Injury and Cognitive Impairment in Vivo and in Vitro Models

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(1)

Published: Jan. 3, 2025

Language: Английский

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Bridging brain and blood: a prospective view on neuroimaging-exosome correlations in HIV-associated neurocognitive disorders

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

HIV-associated neurocognitive disorder (HAND) is a complex neurological complication resulting from human immunodeficiency virus (HIV) infection, affecting about 50% of individuals with HIV and significantly diminishing their quality life. HAND includes variety cognitive, motor, behavioral disorders, severely impacting patients' life social functioning. Although combination antiretroviral therapy (cART) has greatly improved the prognosis for patients, incidence remains high, underscoring urgent need to better understand its pathological mechanisms develop early diagnostic methods. This review highlights latest advancements in neuroimaging exosome biomarkers research. Neuroimaging, particularly magnetic resonance imaging (MRI), offers non-invasive repeatable method monitor subtle changes brain structure function, potentially detecting signs HAND. Meanwhile, exosomes are nano-sized vesicles secreted by cells that serve as key mediators intercellular communication, playing crucial role neuropathology acting critical bridge between peripheral blood central nervous system lesions. Thus, combining plasma indicators derived scans may enhance diagnosis summarizes evidence supporting reliable detection management Furthermore, we emphasize correlation explore potential combined use. discusses technical challenges methodological limitations integrating these two types proposes future research directions. multidisciplinary integrative approach not only promises improve health patients but also offer valuable insights into other neurodegenerative diseases.

Language: Английский

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