Is the Central Nervous System Reservoir a Hurdle for an HIV Cure? DOI Creative Commons
Nazanin Mohammadzadeh, Nicolas Chomont, Jérôme Estaquier

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(12), P. 2385 - 2385

Published: Dec. 5, 2023

There is currently no cure for HIV infection although adherence to effective antiretroviral therapy (ART) suppresses replication of the virus in blood, increases CD4+ T-cell counts, reverses immunodeficiency, and life expectancy. Despite these substantial advances, ART a lifelong treatment people with (PWH) upon cessation or interruption, quickly rebounds plasma anatomic sites, including central nervous system (CNS), resulting disease progression. With recent advances quantifying viral burden, detection genetically intact genomes, isolation replication-competent from brain tissues PWH receiving ART, it has become apparent that CNS reservoir (largely comprised macrophage type cells) poses challenge strategies. Other obstacles impacting curing include ageing populations, substance use, comorbidities, limited drug efficacy cells, ART-associated neurotoxicity. Herein, we review findings, studies proviral integration decay rates, new treatment/prevention strategies context CNS, together highlighting next steps investigations as reservoir.

Language: Английский

Immune Alterations and Viral Reservoir Atlas in SIV-Infected Chinese Rhesus Macaques DOI Creative Commons
Julien Clain,

Morgane Picard,

Henintsoa Rabezanahary

et al.

Infectious Disease Reports, Journal Year: 2025, Volume and Issue: 17(1), P. 12 - 12

Published: Feb. 6, 2025

Background/Objectives: Over the last decades, our projects have been dedicated to clarifying immunopathological and virological events associated with Human Immunodeficiency Virus (HIV) infection. Methods: By using non-human primate models of pathogenic non-pathogenic lentiviral infections, we aimed at identifying cells tissues in which virus persists, despite antiretroviral therapy (ART). Indeed, eradication viral reservoirs is a major challenge for HIV cure. Results: We present series results performed rhesus macaques Chinese origin deciphering immunological ART that can be interest people living HIV. Conclusions: This model could understanding whole body clinical alteration persist ART.

Language: Английский

Citations

0
Fibroblast heterogeneity and its role in generating protective immunity in the secondary lymphoid organs DOI Creative Commons
Hadida Yasmin,

R. Ramesh,

Ann Mary Joseph

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 3, 2025

Fibroblasts are cells of mesenchymal origin with a range phenotypic diversity and heterogeneity. One the major functions fibroblasts is formation turnover extracellular matrix establishing tissue structure by forming matrisome from embryonic development to adult stage. It plays an indispensable role in remodeling during injury, repair, infection, providing scaffold for cell-to-cell interaction. Despite their important pathophysiological roles, molecular markers tissue-resident only now being identified. acquire signatures based on anatomical locations, thus impacting heterogeneity despite overlapping morphology. recognized as key immune sentinel cells, capable regulating inflammatory milieu through distinct functional subsets that designed respond differently unique signatures. can detect pathogenic danger signals diverse pattern recognition receptors (PRRs) release soluble mediators modulate infiltrates at site injury repair. This review discusses secondary lymphoid organs such lymph nodes, spleen, Peyer’s patches, contributions pathological physiological processes. The trans-differentiated effector fibroblast phenotypes expression function various innate components (PRRs, cytokines, chemokines, complement) maintaining homeostasis has also been discussed.

Language: Английский

Citations

0
Navigating the Gene Co-Expression Network and Drug Repurposing Opportunities for Brain Disorders Associated with Neurocognitive Impairment DOI Creative Commons
Mathew Timothy Artuz Manuel, Lemmuel L. Tayo

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(11), P. 1564 - 1564

Published: Nov. 7, 2023

Neurocognitive impairment refers to a spectrum of disorders characterized by decline in cognitive functions such as memory, attention, and problem-solving, which are often linked structural or functional abnormalities the brain. While its exact etiology remains elusive, genetic factors play pivotal role disease onset progression. This study aimed identify highly correlated gene clusters (modules) key hub genes shared across neurocognition-impairing diseases, including Alzheimer's (AD), Parkinson's with dementia (PDD), HIV-associated neurocognitive (HAND), glioma. Herein, microarray datasets AD (GSE5281), HAND (GSE35864), glioma (GSE15824), PD (GSE7621) were used perform Weighted Gene Co-expression Network Analysis (WGCNA) preserved modules studied brain diseases. Through set enrichment analysis, found point towards processes neuronal transcriptional dysregulation, neuroinflammation, protein aggregation, mitochondrial dysfunction, hallmarks many disorders. These constructing protein-protein interaction networks diseases interest. roles homeostasis, cell cycle regulation, energy metabolism, signaling, all associated CNS explored for their drug repurposing experiments. Drug based on signatures highlighted drugs Dorzolamide Oxybuprocaine, modulate expression may have therapeutic implications both traditionally been other medical purposes, our underscores potential combined WGCNA strategy searching new avenues simultaneous treatment different that similarities co-expression networks.

Language: Английский

Citations

5
Is the Central Nervous System Reservoir a Hurdle for an HIV Cure? DOI Creative Commons
Nazanin Mohammadzadeh, Nicolas Chomont, Jérôme Estaquier

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(12), P. 2385 - 2385

Published: Dec. 5, 2023

There is currently no cure for HIV infection although adherence to effective antiretroviral therapy (ART) suppresses replication of the virus in blood, increases CD4+ T-cell counts, reverses immunodeficiency, and life expectancy. Despite these substantial advances, ART a lifelong treatment people with (PWH) upon cessation or interruption, quickly rebounds plasma anatomic sites, including central nervous system (CNS), resulting disease progression. With recent advances quantifying viral burden, detection genetically intact genomes, isolation replication-competent from brain tissues PWH receiving ART, it has become apparent that CNS reservoir (largely comprised macrophage type cells) poses challenge strategies. Other obstacles impacting curing include ageing populations, substance use, comorbidities, limited drug efficacy cells, ART-associated neurotoxicity. Herein, we review findings, studies proviral integration decay rates, new treatment/prevention strategies context CNS, together highlighting next steps investigations as reservoir.

Language: Английский

Citations

1