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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MicroRNAs in HIV infection: dual regulators of viral replication and host immunity

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

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The diverse roles of miRNAs in HIV pathogenesis: Current understanding and future perspectives

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 5, 2023

Despite noteworthy progress made in the management and treatment of HIV/AIDS-related disease, including introduction now almost ubiquitous HAART, there remains much to understand with respect HIV infection. Although some roles that miRNAs play diseases have become more obvious late, context pathogenesis not, as yet, been elucidated, require further investigations. can either be beneficial or harmful host, depending upon genes they target. Some target 3′ UTR viral mRNAs accomplish restriction However, HIV-1 infection, are several dysregulated host which their respective factors facilitate abrogate In this review, we discuss various aspects pathogenesis. We describe detail mechanisms thereby directly indirectly regulate Moreover, predictive life cycle also discussed. Contemporary antiretroviral therapeutic drugs received attention recently, due success HIV/AIDS; therefore, miRNA involvement therapeutics elaborated herein. The potential discussed, propose herein one specific miRNA, miR-34a, warrants exploration, is known three proteins promote Finally, future perspectives controversy around expression by

Language: Английский

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New Therapies and Strategies to Curb HIV Infections with a Focus on Macrophages and Reservoirs

Viruses, Journal Year: 2024, Volume and Issue: 16(9), P. 1484 - 1484

Published: Sept. 18, 2024

More than 80 million people worldwide have been infected with the human immunodeficiency virus (HIV). There are now approximately 39 individuals living HIV/acquired syndrome (AIDS). Although treatments against HIV infection available, AIDS remains a serious disease. Combination antiretroviral therapy (cART), also known as highly active (HAART), consists of treatment combination several drugs that block multiple stages in replication cycle. However, increasing usage cART is inevitably associated emergence drug resistance. In addition, development persistent cellular reservoirs latent critical obstacle to viral eradication since rebound takes place once anti-retroviral (ART) interrupted. Thus, efforts being applied new generations drugs, vaccines and types cART. this review, we summarize antiviral therapies used for HIV/AIDS, both individual agents therapies, highlight role macrophages most recent clinical studies related

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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iPS cell–derived model to study the interaction between tissue macrophage and HIV-1

Journal of Leukocyte Biology, Journal Year: 2023, Volume and Issue: 114(1), P. 53 - 67

Published: March 15, 2023

Abstract Despite effective antiretroviral therapy, HIV-1 persists in cells, including macrophages, which is an obstacle to cure. However, the precise role of macrophages infection remains unclear because they reside tissues that are not easily accessible. Monocyte-derived widely used as a model peripheral blood monocytes cultured and differentiated into macrophages. another needed recent studies revealed most adult originate from yolk sac fetal liver precursors rather than monocytes, embryonic possess self-renewal (proliferating) capacity monocyte-derived lack. Here, we show human induced pluripotent stem cell–derived immortalized macrophage-like cells useful self-renewing macrophage model. They proliferate cytokine-dependent manner, retain functions, support replication, exhibit infected macrophage–like phenotypes, such enhanced tunneling nanotube formation cell motility, well resistance viral cytopathic effect. several differences also observed between can be explained by proliferation cells. For instance, proviruses with large internal deletions, increased over time individuals receiving enriched more rapidly Interestingly, inhibition transcription HIV-1–suppressing agents obvious Collectively, our present study proposes suitable for mimicking interplay tissue newly recognized major population cannot fully modeled alone.

Language: Английский

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The HIV Restriction Factor Profile in the Brain Is Associated with the Clinical Status and Viral Quantities

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 316 - 316

Published: Jan. 23, 2023

HIV-encoded DNA, RNA and proteins persist in the brain despite effective antiretroviral therapy (ART), with undetectable plasma cerebrospinal fluid viral levels, often association neurocognitive impairments. Although determinants of HIV persistence have garnered attention, expression regulation host restriction factors (RFs) for SIV remain unknown. We investigated transcriptomic profile RF genes by RNA-sequencing confirmation qRT-PCR cerebral cortex people who are uninfected (HIV[−]), those HIV-infected without pre-mortem disease (HIV[+]), disorders (HIV[+]/HAND) encephalitis (HIV[+]/HIVE). observed significant increases brains HIV[+]/HIVE load. Machine learning techniques identified MAN1B1 as a key gene that distinguished HIV[+] group from groups HAND. Analyses SIV-associated RFs SIV-infected Chinese rhesus macaques different ART regimens revealed diminished among ART-exposed animals, although interruption resulted an induced several including OAS3, RNASEL, MX2 MAN1B1. Thus, displays distinct is associated neurological status well burden. Moreover, can influence brain’s profile, which might contribute to outcomes.

Language: Английский

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CD34-positive monocytes are highly susceptible to HIV-1

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 28, 2024

Abstract HIV-1 persists in cellular reservoirs despite effective combined antiretroviral therapy (cART). CD4 + T cells are a well-known reservoir, but there is evidence suggesting that myeloid cells, including circulating monocytes, also clinically relevant reservoir. However, it not fully understood which subsets of monocytes preferentially infected vivo. Here, we show monocyte fraction expressing stem cell marker CD34 more susceptible to infection than the CD34-negative major subset. In cART-untreated viremic individuals, increased percentage total and harbored higher copies proviral DNA Consistent with this, expressed receptors CCR5 at levels restriction factors MX2 SAMHD1 lower levels. Interestingly, was still detectable cART-treated virologically suppressed individuals. were present lymph nodes, subset, as observed peripheral blood. Moreover, blood nodes highly CCR7 sphingosine-1-phosphate receptor 1 (S1PR1), critical regulators vivo trafficking. Collectively, our findings raise new possibility node originate from circulation, owing their high susceptibility HIV-1, return explains detection even after long-term cART.

Language: Английский

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Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection

Viruses, Journal Year: 2022, Volume and Issue: 14(10), P. 2218 - 2218

Published: Oct. 9, 2022

In this study, we evaluate the role of MIF/CD74 axis in functionality CD4+ T lymphocytes (CD4TL) during HIV infection. MDMs from healthy donors were infected with a R5-tropic or Transmitted/Founder (T/F) strain. At day 11 post-MDM infection, allogeneic co-cultures uninfected CD4TLs plus MIF stimulus performed. Cytokine production was evaluated by ELISA. plasma levels people (PWH) The phenotype and infection rate PWH analyzed after stimulus. Intracellular cytokines transcription factors flow cytometry. Data parametric non-parametric methods. stimulation HIV-infected induced an increased expression IL-6, IL-1β IL-8. CD4TL/MDM co-cultures, treatment IL-17A/RORγt-expressing CD4TLs. Higher concentrations IL-17A supernatants also observed. These results recapitulated using transmitted/founder HIV-1 strains. appeared to affect memory more than naïve blocking showed negative impact on IL17A+CD4TL proportions. PWH-derived correlated higher IL-17A+CD4TL percentages. Finally, PBMCs led increase Th17-like population. may contribute viral pathogenesis generating microenvironment enriched activating mediators CD4TLs, which are known be highly susceptible relevant persistence. observations establish basis for considering as possible therapeutic target.

Language: Английский

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A Truncated Isoform of Cyclin T1 Could Contribute to the Non-Permissive HIV-1 Phenotype of U937 Promonocytic Cells

Viruses, Journal Year: 2024, Volume and Issue: 16(8), P. 1176 - 1176

Published: July 23, 2024

The different susceptibility to HIV-1 infection in U937 cells-permissive (Plus) or nonpermissive (Minus)-is linked the expression Minus cells of interferon (IFN)-γ inducible antiviral factors such as tripartite motif-containing protein 22 (TRIM22) and class II transactivator (CIITA). CIITA interacts with Cyclin T1, a key component Positive-Transcription Elongation Factor b (P-TEFb) complex needed for efficient transcription upon interaction viral Tat. TRIM22 CIITA, recruiting it into nuclear bodies together T1. A 50 kDa T1 was found only cells, alongside canonical 80 protein. this truncated form remained unaffected by proteasome inhibitors but reduced IFNγ treatment. Unlike full-length protein, also present cytoplasm, subcellular localization correlated its capacity inhibit Tat-mediated transcription. likely contributes their non-permissive phenotype acting dominant negative factor, disrupting P-TEFb formation function. Its reduction treatment suggests regulatory loop which inhibitory role on replication is then exerted IFNγ-induced binds displacing from complex.

Language: Английский

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