The Role of Sustained Type I Interferon Secretion in Chronic HIV Pathogenicity: Implications for Viral Persistence, Immune Activation, and Immunometabolism

Viruses, Journal Year: 2025, Volume and Issue: 17(2), P. 139 - 139

Published: Jan. 22, 2025

Human immunodeficiency virus (HIV) infection induces chronic immune activation by stimulating both the innate and adaptive systems, resulting in persistent inflammation cell exhaustion. Of note, modulation of cytokine production its release can significantly influence response. Type I interferons (IFN-Is) are cytokines that play a crucial role immunity due to their potent antiviral effects, regulation IFN-stimulated genes essential for viral clearance, initiation responses. Thus, an understanding dual IFN-I (protective versus harmful) during HIV-1 infections elucidating contributions HIV pathogenesis is advancing therapeutic interventions. This review therefore delves into intricate involvement acute phases emphasizes impact on persistence, activation, immunometabolism treated HIV-infected individuals.

Language: Английский

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Differential shaping of T cell responses elicited by heterologous ChAd68/self-amplifying mRNA SIV vaccine in macaques in combination with αCTLA4, αPD-1, or FLT3R agonist

The Journal of Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

Abstract While therapeutic vaccines are a promising strategy for inducing human immunodeficiency virus (HIV) control, HIV tested to date have offered limited benefit people living with HIV. The barriers success may include the use of vaccine platforms and/or immunogens that drive weak or suboptimal immune responses, escape dysfunction associated chronic infection despite effective antiretroviral therapy. Combining modulators in safe manner address some challenges and thus increase efficacy vaccines. We evaluated immunogenicity ChAd68/samRNA-based simian (SIV) regimen alone combination series preclinical rhesus macaque (M. mulatta) model. was co-delivered checkpoint inhibitors αPD-1 αCTLA-4, FLT3 receptor agonist (FLT3Ra) shown differentiate expand dendritic cells improve T cell priming. demonstrate magnitude, breadth functionality SIV-specific vaccine-elicited CD8+ responses were enhanced by either αPD-1, FLT3Ra. Combination FLT3Ra also expanded polyfunctional CD4+ responses. Our data distinct shaping implications developing functional cure.

Language: Английский

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Peripheral blood cytokine expression levels and their clinical significance in children with influenza

Translational Pediatrics, Journal Year: 2025, Volume and Issue: 14(2), P. 286 - 297

Published: Feb. 1, 2025

Cytokine levels in the peripheral blood of children infected with influenza A virus are significantly associated disease diagnosis and severity. This study aimed to investigate correlation between expression six cytokines pediatric patients severity their condition. The were measured using a flow cytometric microsphere array. Statistical analysis was performed IBM SPSS Statistics 26.0 compare differences groups, P value less than 0.05 considered statistically significant. Univariate showed that interferon alpha-2 (IFN-α2), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-18 (IL-18) elevated group (P≤0.001). IL-18 higher H3N2 H1N1 (P=0.03), IFN-α2 Mycoplasma coinfection compared influenza-only (P=0.04). Notably, significant MCP-1 observed mild-moderate severe subgroups (P=0.008, P=0.01, respectively). Negative correlations found (r=-0.357, P=0.006 r=-0.329, Multifactorial logistic regression receiver operating characteristic (ROC) curve identified as independent risk factors for A. Inflammatory cytokine critical modulating immune inflammatory responses body. could serve early indicators group, this finding may aid differentiating subtypes, providing insights tailored interventions.

Language: Английский

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Residual immune dysregulation in human immunodeficiency virus infection: implications for hypersensitivity

International Journal of Advances in Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Residual immune dysregulation persists in people living with human immunodeficiency virus (PLWHIV) despite antiretroviral therapy (ART), characterized by chronic activation and imbalances responses that increase the risk of allergic conditions such as drug hypersensitivity, atopic dermatitis (AD), asthma. This literature review explores mechanisms underlying PLWHIV its implications for hypersensitivity reactions. HIV infection shifts response from Th1 to Th2, increasing cytokine production, particularly IL-4 IL-13, elevating IgE levels, contributing Drug especially nevirapine abacavir, occurs more frequently PLWHIV, a higher severe Stevens-Johnson syndrome (SJS) toxic epidermal necrolysis (TEN). The management allergies remains challenging due persistent dysregulation, limited therapeutic options, lack specific clinical guidelines. Understanding these immunological changes is crucial developing better strategies allergy prevention this population.

Language: Английский

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Sex differences in the risk profiles for anemia in people living with HIV, A cross sectional study

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(3), P. e0319611 - e0319611

Published: March 10, 2025

Background Anemia in people living with HIV (PLWH) significantly impacts quality of life and health outcomes. This study aimed to determine sex differences factors associated anemia PLWH at Livingstone University Teaching Hospital, Zambia. Methods cross-sectional involved 631 aged 18 years or older who had been on combinational ART for least 6 months. Data was collected via standardized questionnaires medical records. defined as haemoglobin levels < 13 g/dL men 12 women, based WHO criteria. Logistic regression models assessed the factors, stratified by sex. Results Participants a median age 44 years, female preponderance 64.2%. The overall prevalence 36%, higher females (41.1%) compared males (27.2%) (p 0.001). In females, waist circumference (AOR = 0.97, 95% CI: 0.95-0.99, P 0.018), albumin 0.96, 0.92-0.99, 0.047), NNRTI regimens 2.78, 1.34-5.78, 0.006), microcytosis 3.18, 1.26-8.03, 0.014), hypertension (OR 0.34, 0.13-0.87, 0.024) were linked adjusted analysis but these associations abrogated male Conclusions We found 36% among PLWH, (41%) (27%), including severe forms anemia. Among lower circumference, levels, regimens, microcytosis, blood pressure not males. Further studies are warranted.

Language: Английский

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A Novel Glia-immune humanized mouse model for investigation of HIV CNS infection and neuroinflammation.

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

Published: March 11, 2025

Abstract Although combined antiretroviral therapy (ART) is successful in suppressing viral replication, HIV persists anatomic reservoirs, including the central nervous system (CNS). Current models, such as HSC-reconstituted humanized mice, lack matched human glia brain, limiting insights into CNS infection and pathogenesis. We developed a novel glia-immune mouse model integrating glial cells brain with donor-matched immune reconstitution peripheral blood lymphoid tissues. Neonatal NSG mice were injected intrahepatically Hematopoietic Stem Cells (HSCs) intracranially glia. observed extensive engraftment of all three types (astrocytes, oligodendroglia, microglia-like cells) key regions, cerebral cortex hippocampus. These supported robust HIV-1 replication blood, tissues CNS. HIV-infected exhibited heightened inflammation elevated expression type I interferon-stimulated genes (ISGs) Bulk RNAseq revealed significant transcriptional changes glia, upregulation ISGs, inflammasome-associated genes, downregulation regulators implicated metabolic regulations epigenetic controls. Overall, this allows interrogation transcriptomic neuron-immune interactions, offering infection, pathology, therapeutic strategies targeting reservoirs neuroinflammatory pathways.

Language: Английский

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Immuno-cell metabolic changes in HIV-1 infection

Infectious Diseases & Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Recent research has shown that metabolic processes within immune cells are essential for both human immunodeficiency virus 1 (HIV-1) infection and the response. Throughout HIV-1 infection—from acute stages to chronic viral latency—immune experience shifts in energy demands pathways, paralleling T-cell exhaustion. Dysregulated metabolism compromises cell function, leading dysfunction persistent inflammation. Therefore, alterations constitute a critical mechanism progression This review specifically explores profiles roles of T cells, monocytes-macrophages, dendritic natural killer B at different infection, emphasizing effects on pathways diverse types. These insights offer valuable therapeutic strategies aimed inhibiting replication, restoring controlling disease progression.

Language: Английский

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Synergistic Activity of Second Mitochondrial-Derived Activator of Caspases Mimetic with Toll-like Receptor 8 Agonist Reverses HIV-1-Latency and Enhances Antiviral Immunity

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2575 - 2575

Published: March 13, 2025

HIV-1 infection is successfully treated by antiretroviral therapy; however, it not curative as remains present in the viral reservoir. A strategy to eliminate reservoir relies on reactivation of latent provirus subsequently trigger immune-mediated clearance. Here, we investigated whether activation Toll-like receptor 8 (TLR8) or RIG-I-like (RLR) together with latency reversal agent (LRA) second mitochondrial-derived activator caspases mimetics (SMACm) leads reduction and antiviral immune activation. The TLR8 RLR agonist elicited a robust pro-inflammatory cytokine response PBMCs from both PWH uninfected people. Notably, co-stimulation SMACm specifically enhanced induced well CD8 T cell responses. Ex vivo treatment significantly decreased size inducible reservoir, whereas targeting reduced 50% ex vivo. Although TLR8/RLR agonists further 25% vivo, effectively inducing immunity may help reactivated cells Our findings strongly suggest that LRAs can be used combination for pattern recognition receptors reactivate induce immunity.

Language: Английский

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Diabetes mellitus among HIV patients on ART at Woldia comprehensive specialized hospital, Northeast Ethiopia

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 29, 2025

Abstract Diabetes mellitus (DM) is an emerging comorbidity among people living with HIV receiving antiretroviral therapy (ART), potentially impacting treatment outcomes, including virologic failure. Identifying key determinants of DM in this population crucial for improving patient care. A hospital-based cross-sectional study was conducted from January 01 to May 30, 2024 at Woldia Comprehensive Specialized Hospital, Ethiopia. total 253 patients on ART least six months were randomly selected. Data collected via structured questionnaires, clinical measurements, and medical record reviews. diagnosed the basis a fasting blood glucose level ≥ 126 mg/dl or random plasma 200 mg/dl. Logistic regression models employed identify factors associated DM, reporting adjusted odds ratios (AORs) 95% confidence intervals (CIs). Statistical significance set p < 0.05. The prevalence participants 9.9%. Compared female patients, male had significantly greater risk developing (AOR = 4.29, CI 1.079–17.04). family history nearly 11-fold increased 10.65, 2.82–40.20). Overweight individuals (BMI > 25 kg/m²) sixfold-fold 5.95, 1.56–22.65). Additionally, interruption restarting 6.11, 1.88–19.84). Approximately one ten DM. significant included sex, overweight status, interruption. These findings highlight need routine metabolic screening, targeted interventions continuous monitoring mitigate optimize

Language: Английский

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Glycation metabolites predict incident age-related comorbidities and mortality in older people with HIV

GeroScience, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Abstract Glycation is a class of modifications arising from non-enzymatic reactions reducing sugars with proteins, lipids, and/or DNA, generating advanced glycation end-products (AGEs). AGEs are linked to many age-related comorbidities. In response HIV-1 infection, activated T-cells and macrophages shift their predominate metabolism oxidative phosphorylation glycolysis. Increased glycolytic flux enhances AGE formation, which may increase this prospective, multicenter cohort study antiretroviral therapy treated people HIV, we explored predictive associations by baseline plasma concentrations corresponding detoxification metabolites, incident comorbidities mortality. included dicarbonyl sugars: 3-deoxyglucosone, glyoxal, methylglyoxal. Methylglyoxal-derived metabolites carboxyethyl-arginine, carboxyethyl-lysine, methylglyoxal hydroimidazolone-1. Detoxification reduced oxidized glutathione, the glyoxalase cycle products lactoyl-glutathione lactoyl-Lysine modified proteins. Plasma was collected at entry, in fasting state, assayed liquid chromatography-mass spectroscopy. Incident clinical outcomes diabetes, chronic kidney disease, hypertension, neurocognitive impairment, peripheral neuropathy, frailty, fractures, recurrent falls, all-cause Among 376 participants, higher derived predicted increased risks while 3-deoxyglucosone an risk neuropathy. By contrast, or lactoyl-glutathione, proteins lower These findings support growing experimental evidence potential mitigate declines interventions that reduce glutathione.

Language: Английский

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