An Immunocytochemistry Method to Investigate the Translationally Active HIV Reservoir

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 682 - 682

Опубликована: Янв. 15, 2025

Despite the success of combination antiretroviral therapy (cART) to suppress HIV replication, persists in a long-lived reservoir that can give rise rebounding viremia upon cART cessation. The translationally active consists HIV-infected cells continue produce viral proteins even presence cART. These are implicated resultant cessation and likely contribute chronic immune activation people living with (PLWH) on Methodologies quantify needed. Here, an automated immunocytochemistry (ICC) assay coupled computational image analysis detect intracellular Gag capsid protein (CA) is described (CA-ICC). For this purpose, fixed were deposited microscopy slides by cytospin technique stained antibodies against CA stainer, followed slide digitization. Nuclear staining was used count number specimen, chromogenic signal quantified determine percentage CA-positive cells. In comparative analyses, digital ELISA, qPCR, flow cytometry validate CA-ICC. specificity sensitivity CA-ICC assessed cell line expresses (MOLT IIIB) alongside control (Jurkat) devoid marker, as well peripheral blood mononuclear (PBMCs) from seronegative donors before or after ex vivo infection laboratory strain. further assayed spiking MOLT IIIB into uninfected Jurkat limiting dilutions. those could down 10 per million superior cytometry. To demonstrate application pre-clinical research, bulk PBMCs obtained mouse non-human primate animal models SIV p27, respectively. level associated plasma loads cell-associated measured qPCR evaluate activity small-molecule targeted activator cell-kill (TACK) clinical specimens presented. Overall, offers simple imaging method for specific sensitive detection preparations.

Язык: Английский

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Synthesis and preclinical evaluation of tigilanol tiglate analogs as latency-reversing agents for the eradication of HIV

Science Advances, Год журнала: 2025, Номер 11(4)

Опубликована: Янв. 24, 2025

Tigilanol tiglate (EBC-46) is a selective modulator of protein kinase C (PKC) isoforms that Food and Drug Administration (FDA) approved for the treatment mast cell tumors in canines with up to an 88% cure rate. Recently, it has been FDA soft tissue sarcomas humans. The role EBC-46 and, especially, its analogs efforts eradicate HIV, treat neurological cardiovascular disorders, or enhance antigen density antigen-targeted chimeric receptor–T receptor–natural killer immunotherapies not reported. Enabled by our previously reported scalable synthesis EBC-46, we report herein systematic design, synthesis, evaluation analogs, including those inaccessible from natural source their PKC affinities, ability translocate PKC, nuclear factor κB activity, efficacy reversing HIV latency Jurkat-Latency cells. Leading show exceptional isoform selectivities, functional activities, serving as promising candidates therapeutic applications.

Язык: Английский

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Lipid nanoparticles in antiretroviral therapy: A nanotechnology breakthrough for HIV/AIDS treatment

HIV Medicine, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Abstract Background The development of an effective drug delivery system for the treatment HIV/AIDS is a global challenge. conventional approach, namely highly active antiretroviral therapy (HAART), has increased lifespan patients. While drugs are critical managing HIV/AIDS, they not considered curative treatments and require additional supportive depending on clinical condition. Theoretically, all steps in life cycle HIV potential targets therapy. However, eradication still possible with these approaches account some limitations. Lipid nanoparticles antiretrovirals (ARVs) as primarily lower toxicity ARVs ease scaling up manufacturing, also offer functionalization capabilities, targeted delivery, controlled release profiles load capacity. Methods Data were retrieved from various online electronic resources, including PubMed, Google Scholar Scopus among others. Keywords such ‘lipid nanoparticles’, ‘antiretroviral therapy’, ‘HIV/AIDS’ ‘nanomedicine’ used to formulate search strategies across approximately 106 research review articles. Results Lipid‐based nanoparticles, liposomes, solid lipid nanostructured carriers hybrid have been reported being strategy anti‐HIV drugs. Conclusions This discusses how lipidic can be deliver their target sites manner considers fate within animal body.

Язык: Английский

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Deep Thought on the HIV Cured Cases: Where Have We Been and What Lies Ahead?

Biomolecules, Год журнала: 2025, Номер 15(3), С. 378 - 378

Опубликована: Март 5, 2025

Antiretroviral therapy (ART) can effectively suppress the replication of human immunodeficiency virus (HIV), but it cannot completely eradicate virus. The persistent existence HIV reservoir is a major obstacle in quest for cure. To date, there have been total seven cured cases worldwide. These patients all cleared while undergoing allogeneic stem cell transplantation (allo-HSCT) hematological malignancies. However, these cases, specific mechanism by which allo-HSCT leads to eradication remains unclear, so necessary conduct an in-depth analysis. Due difficulty obtaining donors and risks associated with transplantation, this treatment method not applicable patients. There still need explore new strategies. In recent years, emerging therapies such as neutralizing antibody immunotherapy, chimeric antigen receptor T (CAR-T) therapy, gene editing, antiviral targeting attracted wide attention due their ability inhibit replication. This article first elaborates on nature reservoir, then deeply explores modalities potential success factors finally discusses current novel methods, hoping provide comprehensive feasible strategies achieving cure HIV.

Язык: Английский

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Immuno-cell metabolic changes in HIV-1 infection

Infectious Diseases & Immunity, Год журнала: 2025, Номер unknown

Опубликована: Март 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.

Язык: Английский

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Wikstrol B reactivates latent human immunodeficiency virus (HIV-1) via the nuclear factor-κB (NF-κB) pathway

Phytomedicine, Год журнала: 2025, Номер 141, С. 156667 - 156667

Опубликована: Март 19, 2025

Язык: Английский

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The Possibilities of Finding a Cure for HIV

Advanced Journal of Graduate Research, Год журнала: 2025, Номер 16(1), С. 23 - 37

Опубликована: Апрель 5, 2025

The human immunodeficiency virus (HIV) is a major worldwide health concern, affecting millions of people globally, and when untreated progresses into acquired immune deficiency syndrome (AIDS). With the availability antiretroviral therapy (ART), HIV infection defined as manageable, but not curable, chronic condition. ART inhibits viral replication prevents transmission does eliminate due to latency in memory T cells, exacerbated by rise drug resistant mutations (DRMs), so lifelong treatment monitoring required. In this review, we discuss justifications research approaches towards finding “cure” for i.e. complete elimination or control without need further treatment. two main barriers developing cure are property high mutation rate virus. A few cases have been cured through bone marrow transplants treat acute myeloid leukaemia, where donors had rare CCR5 gene, required entry. More viable include “Shock Kill” method which aims use reverse allowing these cells be detected destroyed with ART, “Block Lock” block transcription HIV-infected latent preventing rebound after cessation ART. possibility vaccination has widely explored, an effective vaccine yet developed more than 40 years pandemic. Currently, appear most favourable, possibly conjunction other recently interventions such passive immunisation broadly neutralizing antibodies. However, taken develop cannot detached from ethical concerns acknowledged navigated.

Язык: 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, Год журнала: 2025, Номер 47(4), С. 273 - 273

Опубликована: Апрель 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

Язык: Английский

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Single cell spatial profiling of FFPE splenic tissue from a humanized mouse model of HIV infection

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Окт. 8, 2024

Latency remains a major obstacle to finding cure for HIV despite the availability of antiretroviral therapy. Due virus dormancy, limited biomarkers are available identify latent HIV-infected cells. Profiling individual cells is needed explore potential latency and study mechanisms persistence that maintain reservoir.

Язык: Английский

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Emerging Crisis: Rise of HIV Through Injectable Drugs Use in Adolescents as a New Pandemic in Tripura, India

Опубликована: Дек. 31, 2024

Язык: Английский

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