Human immunodeficiency virus and oral microbiota: mutual influence on the establishment of a viral gingival reservoir in individuals under antiretroviral therapy DOI Creative Commons
Diana Estefania Ramos Peña, Sylvie Pillet, Alan Grupioni Lourenço

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: April 10, 2024

The role of the oral microbiota in overall health and systemic diseases has gained more importance recent years, mainly due to effects that are mediated by chronic inflammation caused diseases, such as periodontitis, through microbial communities mouth. infection human immunodeficiency virus (HIV) interacts at tissue level (e.g. gut, genital tract, brain) create reservoirs; modulation gut HIV is a good example these interactions. purpose present review assess state knowledge on (microbiome, mycobiome virome) HIV-infected patients comparison HIV-negative individuals discuss reciprocal influence with periodontitis potential establishment viral gingival reservoir. different clinical biological parameters reviewed including age, immune status, potent antiretroviral therapies, smoking, airway coinfections, all factors can modulate during infection. analysis literature proposed this indicates comparisons available studies difficult their great heterogeneity. However, some important findings emerge: (i) less influenced than infection, although recurrent changes microbiome identified many studies; (ii) severe immunosuppression correlated altered therapies correct partially modifications; (iii) constitutes major factor dysbiosis, which exacerbated patients; its pathogenesis be described reinforcement two conditions, where local dysbiosis periodontal pocket leads inflammation, bacterial translocation destruction supporting tissues, turn enhances an inflammatory environment perpetuates cycle. With objective curing reservoirs future it appears develop further researches aimed defining whether inflamed gingiva serve reservoir periodontitis.

Language: Английский

Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study DOI Creative Commons

Yunyu Mao,

Qibin Liao,

Youwei Zhu

et al.

Cell Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 14, 2024

Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing CXCR5, termed M10 cells. were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, B-cell follicle homing. After demonstrating activities, administered treat 18 patients via a regimen two allogenic cell infusions an interval 30 days, each infusion followed by chidamide stimulations reservoir activation. Consequently, 74.3% resulted in significant suppression viral rebound, loads declining average 67.1%, 10 showed persistently reduced cell-associated RNA levels (average decrease 1.15 log10) over 150-day observation period. also found impose selective pressure latent reservoir. No treatment-related adverse observed. Overall, our study supported potential as novel, safe, effective option functional cure HIV-1/AIDS.

Language: Английский

Citations

16
A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication DOI Open Access
Belgin Sever, Masami Otsuka, Mikako Fujita

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3659 - 3659

Published: March 25, 2024

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection a fatal illness into manageable chronic disorder. However, presence of latent reservoirs, multifaceted nature HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict efficacy current cART targeting distinct stages life cycle. Therefore, there unmet need for discovery new therapeutics that not only bypass limitations but also protect body’s at same time. The main goal complete eradication purging latently infected cells patients’ bodies. A potential strategy called “lock-in apoptosis” targets budding phase cycle leads susceptibility apoptosis elimination reservoirs and, ultimately, eradication. work intends present advantages disadvantages United States Food Drug Administration (FDA)-approved anti-HIV-1 drugs as well plausible strategies design development more compounds with better potency, favorable pharmacokinetic profiles, improved safety issues.

Language: Английский

Citations

12
Evaluation of the Potency of Repurposed Antiretrovirals in HBV Therapy: A Narrative Investigation of the Traditional Medicine Alternatives DOI Open Access
Samuel Chima Ugbaja,

Ata Thabo Mokoena,

Aganze Gloire-Aimé Mushebenge

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1523 - 1523

Published: Feb. 11, 2025

Hepatitis B is one of the killer communicable diseases, with a global estimation 1.1 million deaths resulting from liver diseases annually. The search for HBV therapeutics has resulted in repurposing existing antiretrovirals (ARVs) treatment, considering their shared common replication mechanisms. This review aimed at evaluating potencies some repurposed ARVs used analyzing mechanisms viral replications and HIV, investigating potentials traditional medicines as an alternative treatment patients. topical keywords drug repurposing, repositioning, antiretrovirals, hepatitis HBV, natural products, medicines, title, abstract were searched PubMed, Web Science, Google Scholar. advanced included five years, 2019-2024. result was filtered 377 to 110 relevant articles. evaluation reveals that CD4+ T cells are targeted by while targets its associated (cirrhosis hepatocellular carcinoma (HCC)). Furthermore, treatments available only prevent or slow down progression cirrhosis, reduce HCC incidence, can improve quality life increase expectancy; however, they not curative HBV. Traditional medicines/natural product extracts phytochemicals exert anti-HBV effects through different improved therapeutic when combined properly. investigation further consideration silico approach might streamline development but also contribute deeper understanding pathogenesis. Therefore, we recommend integration computational design methods medicine screening discovering new bioactive candidates.

Language: Английский

Citations

1
HIV Tissue Reservoirs: Current Advances in Research DOI
Kangpeng Li, Bo Liu, Rui Ma

et al.

AIDS Patient Care and STDs, Journal Year: 2023, Volume and Issue: 37(6), P. 284 - 296

Published: May 15, 2023

Acquired immunodeficiency syndrome (AIDS), caused by the human virus (HIV), has become a heavy burden of disease and an important public health problem in world. Although current antiretroviral therapy (ART) is effective at suppressing blood, HIV still remains two different types reservoirs-the latently infected cells (represented CD4+ T cells) tissues containing those cells, which may block access to ART, HIV-neutralizing antibodies latency-reversing agents. The latter focus our review, as blood viral load drops below detectable levels after deeper more systematic understanding tissue reservoirs imperative. In this we take lymphoid system (including lymph nodes, gut-associated tissue, spleen bone marrow), nervous system, respiratory reproductive (divided into male female), urinary order, focusing on particularity importance each infection, infection target cell specific situation quantified DNA or RNA evidence compartmentalization pharmacokinetics. summary, found that present state both similarities differences. future, therapeutic principle need follow respect discrepancy basis grasping commonality. measures taken completely eliminate whole body cannot be generalized. It necessary formulate personalized treatment strategies according characteristics various tissues, so realize prospect curing AIDS soon possible.

Language: Английский

Citations

22
Changing epidemiology of COVID-19: potential future impact on vaccines and vaccination strategies DOI Creative Commons

Timo Ulrichs,

Morgane Rolland, Jian Wu

et al.

Expert Review of Vaccines, Journal Year: 2024, Volume and Issue: 23(1), P. 510 - 522

Published: April 24, 2024

COVID-19 was an unprecedented challenge worldwide; however, disease epidemiology has evolved, and no longer constitutes a public health emergency of international concern. Nonetheless, remains global threat uncertainties remain, including definition the end pandemic transition to endemicity, understanding true rates SARS-CoV-2 infection/transmission.

Language: Английский

Citations

8
Recent advances in poor HIV immune reconstitution: what will the future look like? DOI Creative Commons
Wenyuan Zhang, Lianguo Ruan

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 7, 2023

Combination antiretroviral therapy has demonstrated proved effectiveness in suppressing viral replication and significantly recovering CD4 + T cell count HIV type-1 (HIV-1)-infected patients, contributing to a dramatic reduction AIDS morbidity mortality. However, the factors affecting immune reconstitution are extremely complex. Demographic factors, co-infection, baseline level, abnormal activation, cytokine dysregulation may all affect reconstitution. According report, 10–40% of HIV-1-infected patients fail restore normalization function. They referred as immunological non-responders (INRs) who achieve complete have higher mortality rate risk developing other non-AIDS diseases compared with those Heretofore, mechanisms underlying incomplete remain elusive, INRs not effectively treated or mitigated. This review discusses recent progress responsible for summarizes corresponding therapeutic strategies according different improve individual therapy.

Language: Английский

Citations

13
Special Issue “The Role of Toll-Like Receptors (TLRs) in Infection and Inflammation 2.0” DOI Open Access
Ralf Kircheis, Oliver Planz

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9709 - 9709

Published: Sept. 7, 2024

Toll-like receptors (TLRs) are key players in the innate immune system, host’ first-line defense against pathogens [...]

Language: Английский

Citations

5
CRISPR/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for cellular resistant to R5 and X4 tropic HIV-1 DOI Creative Commons
Wannisa Khamaikawin, Chonticha Saisawang, Boonrat Tassaneetrithep

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: May 13, 2024

Abstract Hematopoietic stem-cell (HSC) transplantation using a donor with homozygous mutation in the HIV co-receptor CCR5 (CCR5Δ32/Δ32) holds great promise as cure for HIV-1. Previously, there were three patients that had been reported to be completely cured from infection by this approach. However, finding naturally suitable Human Leukocyte Antigen (HLA)-matched CCR5Δ32 is very difficult. The prevalence of allele only 1% Caucasian population. Therefore, additional sources CCR5Δ32/Δ32 HSCs are required. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas) system one method mediate knockout has successfully employed gene editing tool clinical trials. Additional anti-HIV-1 strategies still required broad-spectrum inhibition HIV-1 replication. Here study, we combined an therapy, which C46, cell membrane-anchored fusion inhibitor CRISPR/Cas9 mediated CCR5. therapeutic genes investigated potential prevention both (R5)- and CXCR4 (X4)-tropic infections MT4CCR5 line. combinatorial therapies superior compared single therapy achieving strategy shows future applications.

Language: Английский

Citations

4
Cell therapies for viral diseases: a new frontier DOI Creative Commons
David Nardo,

Emileigh G. Maddox,

James L. Riley

et al.

Seminars in Immunopathology, Journal Year: 2025, Volume and Issue: 47(1)

Published: Jan. 2, 2025

Abstract Despite advances in medicine and antimicrobial research, viral infections continue to pose a major threat human health. While strides have been made generating vaccines small molecules combat emerging pathogens, new modalities of treatment are warranted diseases where there is lack options, or cannot fully eradicate as HIV infection. Cellular therapies, some which FDA approved for treating cancer, take advantage our developing understanding the immune system, harness this knowledge enhance, direct, responses toward infectious agents. As with viruses that evade immunity, do so by avoiding recognition redirecting cellular would them. such, infusing virus specific cells has potential improve patient outcomes should be investigated tool arsenal fight The present manuscript summarizes key findings using therapies infections, focusing on these strategies might controlling disease.

Language: Английский

Citations

0
Asymmetric distribution of G-quadruplex forming sequences in genomes of retroviruses DOI Creative Commons

Filip Kledus,

Michaela Dobrovolná,

Jean‐Louis Mergny

et al.

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

Published: Jan. 2, 2025

Language: Английский

Citations

0