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

---

TGF-β blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs in vivo

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 14, 2024

Abstract HIV-1 persistence during ART is due to the establishment of long-lived viral reservoirs in resting immune cells. Using an NHP model barcoded SIVmac239 intravenous infection and therapeutic dosing anti-TGFBR1 inhibitor galunisertib (LY2157299), we confirm latency reversal properties vivo TGF-β blockade, decrease stimulate responses. Treatment eight female, SIV-infected macaques on with four 2-weeks cycles leads reactivation as indicated by plasma load immunoPET/CT a 64 Cu-DOTA-F(ab’) 2 -p7D3-probe. Post-galunisertib, lymph nodes, gut PBMC exhibit lower cell-associated (CA-)SIV DNA intact pro-virus (PBMC). Galunisertib does not lead systemic increase inflammatory cytokines. High-dimensional cytometry, bulk, single-cell (sc)RNAseq reveal galunisertib-driven shift toward effector phenotype T NK cells characterized progressive downregulation TCF1. In summary, demonstrate that galunisertib, clinical stage inhibitor, reverses SIV decreases driving phenotype, enhancing responses absence toxicity.

Language: Английский

---

HIV transcription persists in the brain of virally suppressed people with HIV

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(8), P. e1012446 - e1012446

Published: Aug. 8, 2024

HIV persistence in the brain is a barrier to cure, and potentially contributes HIV-associated neurocognitive disorders. Whether transcription persists despite viral suppression with antiretroviral therapy (ART) subject same blocks seen other tissues blood, unclear. Here, we quantified level of transcripts frontal cortex tissue from virally suppressed or non-virally people (PWH). transcriptional profiling (and PBMCs where available) (n = 11) PWH 13) was performed using digital polymerase chain reaction assays (dPCR). CD68+ myeloid cells CD3+ T expressing p24 protein present detected multiplex immunofluorescence imaging. Frontal had TAR 23/24) Long-LTR 20/24) transcripts. Completion evident 12/13 5/11 PWH, p24+CD68+ these individuals. While block proximal elongation both groups, this more extensive PWH. These findings suggest that transcriptionally active reservoir subset

Language: Английский

---

MicroRNAs and long non-coding RNAs during transcriptional regulation and latency of HIV and HTLV

Retrovirology, Journal Year: 2024, Volume and Issue: 21(1)

Published: Feb. 29, 2024

Abstract Human immunodeficiency virus (HIV) and human T cell leukemia (HTLV) have replicative latent stages of infection. The status the viruses is dependent on cells that harbour them different events change transcriptional post-transcriptional events. Non-coding (nc)RNAs are key factors in regulation retrovirus replication cycles. Notably, micro (mi)RNAs long non-coding (lnc)RNAs important regulators can induce switches between active transcription-replication latency retroviruses impacts their pathogenesis. Here, we review functions miRNAs lncRNAs context HIV HTLV. We describe how specific involved viruses’ transcription, latency. further discuss treatment strategies using ncRNAs for HTLV remission, reactivation or possible cure.

Language: Английский

---

Tissue-resident immune cells: from defining characteristics to roles in diseases

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 16, 2025

Tissue-resident immune cells (TRICs) are a highly heterogeneous and plastic subpopulation of that reside in lymphoid or peripheral tissues without recirculation. These endowed with notably distinct capabilities, setting them apart from their circulating leukocyte counterparts. Many studies demonstrate complex roles both health disease, involving the regulation homeostasis, protection, destruction. The advancement tissue-resolution technologies, such as single-cell sequencing spatiotemporal omics, provides deeper insights into cell morphology, characteristic markers, dynamic transcriptional profiles TRICs. Currently, reported TRIC population includes tissue-resident T cells, memory B (BRM) innate lymphocytes, macrophages, neutrophils (TRNs), mast but unignorably existence TRNs is controversial. Previous focus on one specific diseases, however, origins, developmental trajectories, intercellular cross-talks every type not fully summarized. In addition, systemic overview TRICs disease progression development parallel therapeutic strategies lacking. Here, we describe function characteristics all types major diseases. We shed light how to harness offer new targets present burning questions this field.

Language: Английский

---

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

---

Retinoic acid enhances HIV-1 reverse transcription and transcription in macrophages via mTOR-modulated mechanisms

Cell Reports, Journal Year: 2024, Volume and Issue: 43(7), P. 114414 - 114414

Published: June 28, 2024

The intestinal environment facilitates HIV-1 infection via mechanisms involving the gut-homing vitamin A-derived retinoic acid (RA), which transcriptionally reprograms CD4+ T cells for increased replication/outgrowth. Consistently, colon-infiltrating carry replication-competent viral reservoirs in people with (PWH) receiving antiretroviral therapy (ART). Intriguingly, integrative colon macrophages, a pool replenished by monocytes, represents rare event ART-treated PWH, thus questioning effect of RA on macrophages. Here, we demonstrate that enhances R5 but not X4 replication monocyte-derived macrophages (MDMs). RNA sequencing, gene set variation analysis, and HIV interactor NCBI database interrogation reveal RA-mediated transcriptional reprogramming associated metabolic/inflammatory processes resistance/dependency factors. Functional validations uncover post-entry action including SAMHD1-modulated reverse transcription CDK9/RNA polymerase II (RNAPII)-dependent under control mammalian target rapamycin (mTOR). These results support model residing intestine ART-untreated PWH contribute to replication/dissemination an mTOR-sensitive manner.

Language: Английский

---

HIV-1-DNA/RNA and immunometabolism in monocytes: contribution to the chronic immune activation and inflammation in people with HIV-1

EBioMedicine, Journal Year: 2024, Volume and Issue: 108, P. 105338 - 105338

Published: Sept. 11, 2024

Language: Английский

---

Additive Effects of Glutathione in Improving Antibiotic Efficacy in HIV–M.tb Co-Infection in the Central Nervous System: A Systematic Review

Viruses, Journal Year: 2025, Volume and Issue: 17(1), P. 127 - 127

Published: Jan. 17, 2025

Background: HIV and tuberculosis (TB) co-infection poses a significant health challenge, particularly when involving the central nervous system (CNS), where it leads to severe morbidity mortality. Current treatments face challenges such as drug resistance, immune reconstitution inflammatory syndrome (IRIS), persistent inflammation. Glutathione (GSH) has therapeutic potential enhance treatment outcomes by improving antibiotic efficacy, reducing inflammation, mitigating dysfunction. Methods: Relevant studies were identified through systematic searches of PubMed, Elsevier, WHO, related databases. Inclusion criteria focused on preclinical clinical research examining GSH or its precursors in HIV, TB, co-infection, with emphasis microbial control, modulation, CNS-related outcomes. Results: Preclinical showed that improves macrophage antimicrobial function, reduces oxidative stress, limits Mycobacterium (M.tb) growth. Animal models demonstrated reduced bacterial burden lungs, liver, spleen supplementation, along enhanced granuloma stability. Clinical highlighted increased TH1 cytokine production, markers, improved CD4+ T cell counts HIV–M.tb co-infected patients. N-acetylcysteine (NAC), precursor, was shown significantly efficacy first-line TB antibiotics mitigate treatment-associated toxicity. Discussion: shows promise an adjunct therapy for cases CNS, may improve recovery reduce However, evidence is limited small sample sizes lack randomized trials. Future should focus developing CNS-directed formulations evaluating integration into current protocols address dual ultimately patient

Language: Английский

---

An Evaluation on the Role of Non-Coding RNA in HIV Transcription and Latency: A Review

HIV/AIDS - Research and Palliative Care, Journal Year: 2023, Volume and Issue: Volume 15, P. 115 - 134

Published: March 1, 2023

Abstract: The existence of latent cellular reservoirs is recognized as the major barrier to an HIV cure. Reactivating and eliminating “shock kill” or permanently silencing “block lock” reservoir, well gene editing, remain promising approaches, but so far have proven be only partially successful. Moreover, using latency reversing agents drugs pose additional considerations, including ability cause toxicity, a potential lack specificity for HIV, low potency when each agent used alone. RNA molecules, such microRNAs (miRNAs) long non-coding RNAs (lncRNAs) are becoming increasingly important regulators expression. RNA-based approaches combatting represent strategy since both miRNAs lncRNAs more cell-type tissue specific than protein coding genes. Thus, higher targeting reservoir with less overall toxicity can likely achieved. In this review, we summarize current knowledge about expression regulation by encoded in human genome, regulatory molecules genome. We discuss transcriptional post-transcriptional align definition latency, describe that either promote anti-latency properties. Finally, provide perspectives on class targets complexity interactions between different their targets, HIV. Keywords: micro RNA, transcripts,

Language: Английский

---