Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 288 - 288

Published: Feb. 13, 2024

Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target HIV-1, their specific roles pathophysiology infection initially largely neglected. However, numerous studies performed over past decade, both vitro cell culture systems vivo monkey humanized mouse animal models, led growing evidence that play important direct indirect HIV-1 pathogenesis. It has been recently proposed are likely involved all stages pathogenesis, virus transmission dissemination, but above all, viral persistence through establishment, together with latently infected reservoirs many host tissues, major obstacle eradication people living HIV. Infected indeed found, very often multinucleated giant expressing antigens, almost lymphoid non-lymphoid tissues HIV-1-infected patients, where they can probably persist for long period time. In addition, also participate, directly targets or indirectly key regulators innate immunity inflammation, chronic inflammation associated clinical disorders observed HIV, even patients receiving effective antiretroviral therapy. The main objective this review is therefore summarize recent findings, revisit older data, regarding critical functions infection, found well during different

Language: Английский

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HIV-1 cell-to-cell infection of macrophages escapes type I interferon and host restriction factors, and is resistant to antiretroviral drugs

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(4), P. e1013130 - e1013130

Published: April 28, 2025

HIV-1-infected macrophages participate in viral transmission, dissemination, and establishment of tissue virus reservoirs. Despite counteracting proteins (Vif, Vpu, Vpr Nef), cell-free macrophage infection is restricted by host cell factors, including those induced interferons. Here, we show that these type I interferon do not influence HIV-1 cell-to-cell transfer to cell-cell fusion with infected T cells, still leading the formation multinucleated giant cells (MGCs). Accordingly, depletion SERINC5 APOBEC3G alter spreading virus-producing MGCs. We further nuclei derived from remains transcriptionally active MGCs may explain resistance restriction factors antiretroviral drugs. Unexpectedly, detect DNA myeloid shortly after initial macrophages. Together, findings unravel how escapes cellular independently auxiliary proteins, while displaying

Language: Английский

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Activation-neutral gene editing of tonsillar CD4 T cells for functional studies in human ex vivo tonsil cultures

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(1), P. 100685 - 100685

Published: Jan. 1, 2024

The molecular and immunological properties of tissue-resident resting CD4 T cells are understudied due to the lack suitable gene editing methods. Here, we describe ex vivo culture methodology ediTONSIL for from human tonsils. Optimized CRISPR-Cas9 RNP nucleofection results in knockout efficacies over 90% without requiring exogenous activation. Editing can be performed on multiple cell types bulk cultures or isolated that labeled reintroduced into their tissue environment. Importantly, maintain tissue-specific such as viability, activation state, immunocompetence following reassembly lymphoid aggregates. This highly efficient versatile workflow tonsillar enables dissection mechanisms adapted other tonsil-resident types.

Language: Английский

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Lymphoid and CXCR4 Cell Targeted Lipid Nanoparticles Facilitate HIV-1 Proviral DNA Excision

Published: Jan. 1, 2025

Language: Английский

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The Possibilities of Finding a Cure for HIV

Advanced Journal of Graduate Research, Journal Year: 2025, Volume and Issue: 16(1), P. 23 - 37

Published: April 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.

Language: Английский

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Humanized Mouse Systems to Study Viral Infection: A New Era in Immunology Research

Annual Review of Immunology, Journal Year: 2025, Volume and Issue: 43(1), P. 143 - 167

Published: April 25, 2025

For decades, scientists have relied on traditional animal models to study viral infection and the immune response. However, these limitations, search for more accurate reliable ways human-pathogen interphase has led development of humanized mouse systems. These revolutionary transformed how we understand human system's interactions with viruses control or exacerbate disease. They are also paving way new treatments therapies. In this article, explore history systems their advantages, applications in immunology research. We describe different types models, including generation utility studying pathogens, an emphasis human-specific viruses. addition, discuss areas further refinement future applications.

Language: Английский

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Accelerated Neuroimmune Dysfunction in Aged HIV-1-Infected Humanized Mice

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 149 - 149

Published: Jan. 23, 2024

Disordered immunity, aging, human immunodeficiency virus type one (HIV-1) infection, and responses to antiretroviral therapy are linked. However, how each factor is linked with the other(s) remains incompletely understood. It has been reported that accelerated advanced HIV-1 inflammation, host genetic factors associated cellular, mitochondrial, metabolic alterations. underlying mechanism elusive. With these questions in mind, we used chronically HIV-1-infected CD34-NSG humanized mice (hu-mice) model older people living HIV uncover associations between infection aging. Adult were infected at age of 20 weeks maintained for another 40 before sacrifice. Animal brains collected subjected transcriptomics, qPCR, immunofluorescence assays immune disease-based biomarkers. CD4+ T cell decline was viral level age. Upregulated C1QA, CD163, CXCL16 downregulated LMNA CLU identified as age-associated genes tied infection. Ingenuity pathway analysis affirmed links innate activation, pyroptosis signaling, neuroinflammation, mitochondrial dysfunction, cellular senescence, neuronal dysfunction. In summary, a valuable studying HIV-1-associated Biomarkers senescence signaling both age- virus-associated. By exploring biological mechanisms biomarkers, interventions next generation patients can be realized.

Language: Английский

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HIV Protein Nef Induces Cardiomyopathy Through Induction of Bcl2 and p21

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11401 - 11401

Published: Oct. 23, 2024

HIV-associated cardiovascular diseases remain a leading cause of death in people living with HIV/AIDS (PLWHA). Although antiretroviral drugs suppress the viral load, they fail to remove virus entirely. HIV-1 Nef protein is known play role virulence and HIV latency. Expression can be detected different organs, including cardiac tissue. Despite established replication, its impact on organ function inside human body not clear. To understand effect at level, we created new Nef-transgenic (Nef-TG) mouse that expresses heart. Our study found expression caused inhibition pathological changes heart increased fibrosis, failure early mortality. Further, cellular autophagy significantly inhibited tissue Nef-TG mice. Mechanistically, causes accumulation Bcl2 Beclin-1 proteins tissue, which may affect system. Additionally, upregulation senescence marker p21 senescence-associated β-galactosidase expression. findings suggest Nef-mediated induction markers promote aging PLWHA. model could help us during latent infection.

Language: Английский

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Theranostics for Viral Infections

NeuroImmune Pharmacology and Therapeutics, Journal Year: 2024, Volume and Issue: unknown, P. 617 - 637

Published: Jan. 1, 2024

Language: Английский

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Humanized mice for studying HIV latency and potentially its eradication

Current Opinion in HIV and AIDS, Journal Year: 2024, Volume and Issue: 19(3), P. 157 - 167

Published: March 27, 2024

Purpose of the review The quest for an HIV cure faces a formidable challenge: persistent presence latent viral infections within cells and tissues infected individuals. This provides thorough examination discussions surrounding latency, use humanized mouse models, strategies aimed at eliminating reservoir. It explores hurdles advancements in understanding pathogenesis, mainly focusing on establishing reservoirs CD4 + T macrophages. Introducing concepts functional sterile cures, underscores indispensable role models research, offering crucial insights into efficacy cART ongoing pursuit cure. Recent findings Here, we highlight studies investigating molecular mechanisms pathogenesis related to latency mice discuss novel eradicating HIV. Emphasizing importance analytical interruption gauge its impact reservoir accurately, underlines progress challenges harnessing research. Summary suggests that provide valuable potential eradication strategies, contributing significantly

Language: Английский

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