Mechanisms and Cardiorenal Complications of Chronic Anemia in People with HIV

Viruses, Journal Year: 2024, Volume and Issue: 16(4), P. 542 - 542

Published: March 30, 2024

Chronic anemia is more prevalent in people living with HIV (PLWH) compared to the general population. The mechanisms that drive chronic are multifaceted and include functional impairment of hematopoietic stem cells, dysregulation erythropoietin production, persistent immune activation. inflammation from infection adversely affects erythropoiesis, erythrocyte lifespan, response, leading a heightened risk co-infections such as tuberculosis, severe anemia, increased mortality. Additionally, exacerbates progression HIV-associated nephrotoxicity contributes cardiovascular through activation inflammation. This review highlights cardinal role link connecting complications PLWH, emphasizing need for universal understanding these interconnected pathways targeted interventions.

Language: Английский

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Microglial- neuronal crosstalk in chronic viral infection through mTOR, SPP1/OPN and inflammasome pathway signaling

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 5, 2024

HIV-infection of microglia and macrophages (MMs) induces neuronal injury chronic release inflammatory stimuli through direct indirect molecular pathways. A large percentage people with HIV-associated neurologic psychiatric co-morbidities have high levels circulating molecules. Microglia, given their susceptibility to HIV infection long-lived nature, are reservoirs for persistent infection. MMs neurons possess the machinery detect pathogen nucleic acids proteins activate innate immune signals. Full activation inflammasome assembly expression IL-1β requires a priming event second signal. Many studies demonstrated that alone can activity. Interestingly, secreted phosphoprotein-1 ( SPP1 /OPN) is highly upregulated in CNS infected dysfunction. all evidence thus far suggests protective function signaling mammalian target rapamycin (mTORC1/2) pathway counter HIV-neuronal injury. Moreover, HIV-infected mice knocked down show by neuroimaging, increased neuroinflammation compared controls. This uses unique regulatory mechanisms control level signaling. In this mini review, we discuss known yet-to-be discovered biological links between -mediated stimulation mTOR Additional new mechanistic insights from relevant experimental models will provide greater understanding crosstalk regulation homeostasis.

Language: Английский

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NLRP3 Inflammasomes: Dual Function in Infectious Diseases

The Journal of Immunology, Journal Year: 2024, Volume and Issue: 213(4), P. 407 - 417

Published: Aug. 5, 2024

Abstract The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has been the most distinctive polymer protein complex. After recognizing endogenous and exogenous danger signals, NLRP3 can cause inflammation by pyroptosis secretion of mature, bioactive forms IL-1β IL-18. is essential in genesis progression infectious illnesses. Herein, we provide a comprehensive review diseases, focusing on its two-sided effects. As an part host defense with protective impact, abnormal activation, however, result systemic high inflammatory response, leading to subsequent damage. In addition, scientific evidence small molecules, biologics, phytochemicals acting reviewed. We believe that helps us understand pathological mechanism different stages diseases inhibitors targeting will become new valuable research direction for treatment diseases.

Language: Английский

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Human cytomegalovirus infection activates NLRP3 inflammasome by releasing mtDNA into the cytosol in human THP‐1 cells

Microbiology and Immunology, Journal Year: 2023, Volume and Issue: 67(6), P. 303 - 313

Published: March 18, 2023

Human cytomegalovirus (HCMV) infection of monocytes results in the production inflammatory cytokine through inflammasome. However, mechanism NLR family pyrin domain containing 3 (NLRP3) inflammasome activation HCMV remains unclear. In this study, promoted increase mitochondrial fusion and caused dysfunction THP-1 cells, including excessive reactive oxygen species decreased membrane potential (Δψm). Meanwhile, expression DNA (mtDNA)-binding protein TFAM (transcription factor A, mitochondrial) was mtDNA content cytoplasm increased. Knockdown an copy number resulted elevated NLRP3 expression, active caspase-1, mature IL-1β. After a h treatment with MCC950, inhibitor, cleaved caspase-1 IL-1β were suppressed. Besides, overexpression inhibited NLRP3, addition, knockdown process after infection. mtDNA-deficient cells showed limited ability to produce conclusion, increased release into cytoplasm, which eventually led

Language: Английский

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Cenicriviroc prevents dysregulation of astrocyte/endothelial cross talk induced by ischemia and HIV-1 via inhibiting the NLRP3 inflammasome and pyroptosis

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 326(2), P. C487 - C504

Published: Dec. 25, 2023

Blood-brain barrier (BBB) breakdown is one of the pathophysiological characteristics ischemic stroke, which may contribute to progression brain tissue damage and subsequent neurological impairment. Human immunodeficiency virus (HIV)-infected individuals are at greater risk for stroke due diminished immune function HIV-associated vasculopathy. Studies have shown that astrocytes involved in maintaining BBB integrity facilitating HIV-1 infection brain. The present study investigated whether targeting astrocyte-endothelial cell signaling with cenicriviroc (CVC), a dual chemokine receptor (CCR)2 CCR5 antagonist, protect against dysregulation cross talk between these cells after oxygen-glucose deprivation/reoxygenation (OGD/R) combined infection. Permeability assay 10 kDa fluorescein isothiocyanate (FITC)-dextran demonstrated CVC alleviated endothelial disruption noncontact coculture human microvascular (HBMECs) HIV-1-infected astrocytes, reversed downregulation tight junction protein claudin-5 induced by OGD/R- HIV-1. Moreover, attenuated HIV-1-triggered upregulation NOD-like protein-3 (NLRP3) inflammasome IL-1β secretion. Treatment also suppressed astrocyte pyroptosis attenuating cleaved caspase-1 levels formation N-terminal GSDMD (N-GSDMD). Secretome profiling revealed ameliorated secretion CC ligand 17 (CCL17), adhesion molecule intercellular molecule-1 (ICAM-1), T activation modulator immunoglobulin mucin domain 3 (TIM-3) synergistically OGD/R Overall, results suggest contributes restoring interactions an astrocyte-dependent manner via protection NLRP3 pyroptosis.

Language: Английский

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Utilization of immunological ratios in HIV: Implications for monitoring and therapeutic strategies

Medicine, Journal Year: 2024, Volume and Issue: 103(9), P. e37354 - e37354

Published: March 1, 2024

Human immunodeficiency virus (HIV) infection remains a significant global health concern, necessitating ongoing research and innovation in the quest for improved disease management. Traditional markers monitoring HIV progression effectiveness of antiretroviral therapy have limitations capturing intricate immune responses inflammatory dynamics people with HIV. In recent years, concept inflammation ratios has gained prominence as valuable tool assessing understanding complex interplay between inflammation, function, this abstract, we provide an overview emerging field utilizing context its implications therapeutic strategies. These ratios, such CD4/CD8 ratio, neutrophil-to-lymphocyte monocyte-to-lymphocyte offer more comprehensive assessment individual's status state. By exploring clinical including their potential to predict complications guide personalized treatment approaches, publication sheds light on benefits incorporating into routine care. Furthermore, emphasize importance further refine our utility significance improving lives

Language: Английский

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Genetic Variants in the NOD-like Receptor Signaling Pathway Are Associated with HIV-1/AIDS in a Northern Chinese Population

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3484 - 3484

Published: April 8, 2025

The NOD-like receptor (NLR) signaling pathway may influence human immunodeficiency virus (HIV) clearance and CD4+ T cell recovery through inflammatory responses, but its specific mechanism requires further investigation. A deeper understanding of genetic variations can provide new insights into the biological mechanisms underlying occurrence development syndrome (AIDS). By utilizing multiple bioinformatic analyses functional annotations, we identified single-nucleotide polymorphisms (SNPs) in NLR that affect HIV-1 infection AIDS progression. Then, a case-control study was performed to screen risk-related variants by genotyping candidate SNPs sample 500 men who have sex with (MSM) healthy controls from Han population Northern China. results revealed significant association between five (NLRP3 rs4612666, MAVS rs17857295, rs6084497, rs16989000, JAK1 rs4244165) infection. Interestingly, gene-gene interaction model composed exhibited cumulative effect on disease. Specially, increase risk alleles carried samples elevated contracting HIV-1. In addition, three (IL1B rs1143623, STAT1 rs1467199 rs2066804) were associated counts patients AIDS. Three (OAS1 rs1131454, NLRP3 rs10754558, rs867335) found be related clinical staging This finding provides genes progression among MSM

Language: Английский

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The Hallmarks of Ageing in Human Immunodeficiency Virus Infection and the Impact of Antiretroviral Therapy on Telomeres: A Molecular Perspective

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 273 - 273

Published: April 12, 2025

Ageing is a complex and unavoidable physiological process which, in simple terms, consists of progressive deterioration the functionality cells, tissues organs, culminating an increased risk developing chronic pathologies. Telomeres, repetitive nucleotide structures at end chromosomes, ensure genomic integrity modulate cellular senescence. The shortening telomere length with each cell division directly correlates susceptibility to However, this shortening, normally inevitable, can be markedly accelerated presence infections, such as HIV-1 infection, by sustained continuous activation immune system, inflammation, generation oxidative stress, or direct alterations produced viral proteins. Thus, narrative review, we discuss 12 hallmarks ageing context understanding molecular changes induced through these well-established pillars could provide holistic approach management HIV-positive patients. At same time, considering that telomeres are centre all changes, assessment impact antiretroviral therapy on necessary guide clinical decisions. ultimate goal research develop personalised therapies increase quality life health outcomes HIV

Language: Английский

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A Distinct Form of Subcutaneous Fat Fibrosis is Linked to Insulin Resistance in People with HIV

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: May 14, 2025

People with HIV (PWH) are at heightened risk for type 2 diabetes (T2D) and insulin resistance (IR), even effective antiretroviral therapy (ART). Adipose tissue dysfunction, including subcutaneous adipose (SAT) fibrosis, is a key contributor to metabolic disease. However, the role of SAT fibrosis in IR among PWH remains poorly understood. We therefore investigated relationship between along molecular signatures that might distinguish HIV-associated from associated obesity. studied 112 participants, 43 69 people without (PWoH) excluding those established T2D. Body composition was assessed by dual-energy X-ray absorptiometry (DXA), analyzed quantifying hydroxyproline levels biopsies. transcriptional profiles were examined using targeted fibrosis-related gene panel. Plasma endotrophin, marker extracellular matrix remodeling, also measured. had significantly greater compared PWoH, largest differences observed participants In this subgroup, strongly IR, despite absence elevated adiposity. Transcriptomic analysis identified distinct fibrosis-associated expression pattern PWH, marked upregulation COL14A1 immune-related genes (e.g. CCL4 , NLRP3 ). Pathway further supported upregulated remodeling immune activation, downregulated thermogenesis, lipid metabolism, signaling non-obese PWH. endotrophin independently fibrosis. Our findings identify as an obesity-independent driver Notably, predicts normal body fat can be noninvasively monitored through circulating offering potential biomarker early intervention. The signature reveals unique mechanisms may underlie population highlight new therapeutic avenues targeting dysfunction. This work National Institutes Health grants R01DK141041 (PWH SKK), R01DK112304 R56DK133997 K08DK124679 (DLA) Robert Wood Johnson Foundation, Harold Amos Medical Faculty Development Program (DLA), NIH T32 Training Grant 5T32DK007418 (MKC), UCSF NORC grant (P30DK098722), Health: UCSF-Bay Area Center AIDS Research (P30 AI027763). funding authorities no study design, data collection, analysis, interpretation, decision publish, or manuscript preparation.

Language: Английский

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Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen

BMC Infectious Diseases, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 3, 2024

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on lifestyle people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated efficacy, safety sustained virologic response two drugs regimens, in particular dolutegravir (DTG). The effects deintensification inflammatory settings are currently unknown PLWH. Thus, our study explored state virologically suppressed HIV individuals between patients treatment a DTG-containing dual (2DR) versus triple regimen therapies (3DR). We enrolled total 116 subjects 2DRs or 3DRs plasma levels pro- anti-inflammatory cytokines (in IL-1β, IL-10, IL-18, IL-33, IL-36 IFN-γ) have been evaluated. CD4 + cell's median value was 729.0 cell/µL 3DR group 771.5 2DR group; viral load negative all patients. Significant differences were found IL-18 (648.8 vs. 475.0 group, p = 0.034) (281.7 247.0 0.050), correlation (rho 0.266, 0.015). This single-center retrospective pharmacological confirms absence significant IFN-γ two-drug regimens compared to regimens. Patients show greater control over serum levels, related an increased cardiovascular risk development age-related chronic diseases. Based results, we suggest that DTG-based could be associated better inflammation characterizes population effective ART.

Language: Английский

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