Compensatory reactions of B cells in response to chronic HIV‐1 Tat exposure DOI Creative Commons
Anna A. Valyaeva,

Maria A. Tikhomirova,

Jun-yi Feng

et al.

Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: 240(1)

Published: Oct. 7, 2024

Patients infected with human immunodeficiency virus-1 (HIV-1) have an increased incidence of B-cell lymphoma, even though HIV-1 does not infect B cells. The development lymphomas appears to be related the action transactivator protein (Tat), which is released from HIV-infected cells and penetrates uninfected cells, affecting host cell gene expression. Upon chronic infection, Tat acts on for a long time, probably allowing adapt presence viral protein. aim this work was identify study mechanism adaptation prolonged (chronic) exposure Tat. We performed comparative analysis expressing under either inducible promoter or constitutive promoter, us model acute effects, respectively. found that leads suppression proliferation, due downregulation genes associated replication synthesis. In case Tat, proliferation restored expression implementation protective (antiviral) functions increased. Analysis using proteasome inhibitors showed in action, intense proteolysis occurred, could main adaptation. Thus, powerful entry efficiency may determine frequency lymphomagenesis HIV-1-infected patients.

Language: Английский

Current status of mannose receptor-targeted drug delivery for improved anti-HIV therapy DOI
Satish Rojekar, Amol D. Gholap, Namdev Togre

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 372, P. 494 - 521

Published: June 27, 2024

Language: Английский

Citations

15
MicroRNAs in HIV infection: dual regulators of viral replication and host immunity DOI
Reda Mansour, Gharieb S. El‐Sayyad,

Nehal I. Rizk

et al.

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

Published: March 3, 2025

Language: Английский

Citations

1
The Hallmarks of Ageing in Human Immunodeficiency Virus Infection and the Impact of Antiretroviral Therapy on Telomeres: A Molecular Perspective DOI Creative Commons

Miruna-Maria Apetroaei,

Stella Baliou, Πέτρος Ιωάννου

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 273 - 273

Published: April 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

Language: Английский

Citations

0
Beyond Infection: The Role of Secreted Viral Proteins in Pathogenesis, Disease Severity and Diagnostic Applications DOI Creative Commons

Luis Herrera-Moro Huitron,

Víctor Javier Cruz-Holguín,

José Manuel Ulloa-Aguilar

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(9), P. 624 - 624

Published: April 22, 2025

Secreted viral proteins are crucial in virus–host interactions, as they modify the host microenvironment to promote infection. These secreted could alter immune and inflammatory responses, allowing viruses evade defense mechanisms such cytotoxic T cell activation antibody neutralization. Some mimic molecules suppress antiviral making them valuable targets for antivirals diagnostics. Notable examples include BARF1 from Epstein–Barr virus, associated with gastric cancer; vIL-10 which regulates responses contributes autoimmune diseases; NS1 dengue vascular permeability early diagnosis; NSP4 rotavirus an enterotoxin, among others. The study of these improves our understanding pathogenesis helps develop innovative treatments infectious non-infectious diseases, taking advantage evolutionary adaptations viruses. This review explores their impact on infection cycle, disease progression, key processes, cycle regulation, apoptosis, signaling. Research deepens basic knowledge virology generates alternative methods detecting biomarkers creating more effective therapies, well implementing some emerging technologies, biosensors plasmon resonance, diagnosis diseases.

Language: Английский

Citations

0
HIV-Tat upregulates the expression of senescence biomarkers in CD4+ T-cells DOI Creative Commons
Víctor Casanova,

Andrea Rodríguez-Agustín,

Rubén Ayala-Suárez

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 24, 2025

Current antiretroviral therapy (ART) for HIV infection reduces plasma viral loads to undetectable levels and has increased the life expectancy of people with (PWH). However, this lifespan is accompanied by signs accelerated aging a higher prevalence age-related comorbidities. Tat (Trans-Activator Transcription) key protein replication pathogenesis. encoded 2 exons, full-length ranging from 86 101 aa (Tat101). Introducing stop codon in position 73 generates 1 exon, synthetic 72aa (Tat72). Intracellular, activates NF-κB pro-inflammatory pathway increases antiapoptotic signals ROS generation. These effects may initiate cellular senescence program, characterized cell cycle arrest, altered metabolism, senescence-associated secretory phenotype (SASP) mediator release precise role HIV-Tat inducing program CD4+ T-cells currently unknown. Jurkat Tetoff lines stably transfected Tat72, Tat101, or an empty vector were used. Flow cytometry RT-qPCR used address biomarkers, 105 mediators assessed supernatants antibody-based membrane array. Key results obtained Jurkat-Tat cells addressed primary, resting transient electroporation HIV-Tat-FLAG plasmid DNA. In model, expression Tat101 biomarkers BCL-2, CD87, p21, sCD30, PDGF-AA, sCD31, among other factors. upregulated CD30 CD31 co-expression surface, distinguishing these Tat72 Jurkats. The percentage p21+, p16+, γ-H2AX+ Tat-expressing T-cells, detected as FLAG+ population compared their FLAG- (Tat negative) counterparts. Increased sCD31 sCD26 also electroporated T-cell supernatants. several SASP/Aging Intracellular contributing premature observed PWH.

Language: Английский

Citations

0
TLR7 Mediates HIV‐1 Tat‐Induced Cellular Senescence in Human Astrocytes DOI Creative Commons

Neda Rezagholizadeh,

Gaurav Datta,

Wendie A. Hasler

et al.

Aging Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

ABSTRACT Cellular senescence contributes to accelerated aging, neuroinflammation, and the development of HIV‐associated neurocognitive disorders (HAND) in era combined antiretroviral therapy (cART). One HIV viral factor that could lead cellular is persistence HIV‐1 Tat brain. As a secreted protein, known enter endolysosomes cells through receptor‐mediated endocytosis, we have shown induces endolysosome damage dysfunction. Significantly, dysfunction has been strongly linked senescence. However, it not whether represents driver or consequence Because Tat‐induced an early step exogenous senescence, tested hypothesis via endolysosome‐dependent mechanism human astrocytes. We demonstrated interacts with endolysosome‐resident Toll‐like receptor 7 (TLR7) its arginine‐rich basic domain, such interaction results senescence‐like phenotype including cell cycle arrest, enhanced SA‐β‐gal activity, increased release senescence‐associated secretory (SASP) factors (IL‐6, IL‐8, CCL2). Thus, our finding provided mechanistic insights whereby provide compelling evidence drives Our findings also highlight novel role TLR7 suggest therapeutic target against HAND.

Language: Английский

Citations

0
SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes DOI Creative Commons

Neda Rezagholizadeh,

Gaurav Datta,

Wendie A. Hasler

et al.

Life Science Alliance, Journal Year: 2025, Volume and Issue: 8(7), P. e202503231 - e202503231

Published: May 5, 2025

Cellular senescence contributes to accelerated aging and the development of various neurodegeneration disorders including HIV-associated neurocognitive disorders. The is attributed, at least in part, CNS persistence HIV-1 transactivator transcription (Tat), an essential protein for viral that actively secreted from HIV-1–infected cells. Secreted Tat enters cells via receptor-mediated endocytosis induces endolysosome dysfunction cellular Given represents early step exogenous Tat-induced senescence, we tested hypothesis endolysosome-dependent mechanism human astrocytes. We demonstrated internalized interacts with endolysosome-resident arginine sensor SLC38A9 arginine-rich basic domain. Such interaction between leads dysfunction, enhanced LTR transactivation, senescence. These findings suggest drives highlight novel role astrocyte

Language: Английский

Citations

0
The Disorderly Nature of Caliciviruses DOI Creative Commons
Vivienne L. Young,

Alice M. McSweeney,

Matthew Edwards

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(8), P. 1324 - 1324

Published: Aug. 19, 2024

An intrinsically disordered protein (IDP) or region (IDR) lacks has little structure but still maintains function. This lack of creates flexibility and fluidity, allowing multiple conformations potentially transient interactions with more than one partner. Caliciviruses are positive-sense ssRNA viruses, containing a relatively small genome 7.6-8.6 kb have broad host range. Many viral proteins known to contain IDRs, which benefit smaller genomes by expanding the functional proteome through multifunctional nature IDR. The percentage residues within total for each calicivirus type species can range between 8 23%, IDRs been experimentally identified in NS1-2, VPg RdRP proteins. not well conserved across genera, whether this correlates different activities increased tolerance mutations, driving virus adaptation new selection pressures, is unknown. function norovirus NS1-2 yet fully elucidated includes involvement cell tropism, promotion spread suppression interferon-λ responses. These functions presence cell-like linear motifs that interact caspases VAPA/B all found affected NS1-2. involved transcription translation, RNA binding, nucleotidylylation cycle arrest, N-terminal IDR human could drive liquid-liquid phase separation. review identifies summarises

Language: Английский

Citations

2
Comprehensive Insights into the Molecular Basis of HIV Glycoproteins DOI Creative Commons
Amir Elalouf, Hanan Maoz,

Amit Yaniv Rosenfeld

et al.

Applied Sciences, Journal Year: 2024, Volume and Issue: 14(18), P. 8271 - 8271

Published: Sept. 13, 2024

Human Immunodeficiency Virus (HIV) is a diploid, C-type enveloped retrovirus belonging to the Lentivirus genus, characterized by two positive-sense single-stranded RNA genomes, that transitioned from non-human primates humans and has become globally widespread. In its advanced stages, HIV leads Acquired Immune Deficiency Syndrome (AIDS), which severely weakens immune system depleting CD4+ helper T cells. Without treatment, progressively impairs function, making body susceptible various opportunistic infections complications, including cardiovascular, respiratory, neurological issues, as well secondary cancers. The envelope glycoprotein complex (Env), composed of gp120 gp41 subunits derived precursor gp160, plays central role in cycle entry. synthesized rough endoplasmic reticulum, undergoes glycosylation proteolytic cleavage, forming trimeric spike on virion surface. These structural features, transmembrane domain (TMD), membrane-proximal external region (MPER), cytoplasmic tail (CT), are critical for viral infectivity evasion. Glycosylation processing, especially furin, essential Env’s fusogenic activity capacity evade detection. virus’s outer glycoprotein, gp120, interacts with host cell CD4 receptors. This interaction, along involvement coreceptors CXCR4 CCR5, prompts exposure components, enabling fusion membranes. While this predominant pathway entry, alternative mechanisms involving receptors such lectin mannose have been found. review aims provide an in-depth analysis features functional roles entry proteins, particularly gp41, process. By examining these proteins’ architecture, elucidates how their properties facilitate invasion It also explores synthesis, trafficking, characteristics Env/gp160 highlighting interactions between matrix. contributions advance drug resistance management vaccine development efforts.

Language: Английский

Citations

2
Heterologous DNA Prime/Protein Boost Immunization Targeting Nef-Tat Fusion Antigen Induces Potent T-cell Activity and in vitro Anti-SCR HIV-1 Effects DOI
Leila Sadeghi, Azam Bolhassani, Elham Mohit

et al.

Current HIV Research, Journal Year: 2024, Volume and Issue: 22(2), P. 109 - 119

Published: March 1, 2024

Heterologous combinations in vaccine design are an effective approach to promote T cell activity and antiviral effects. The goal of this study was compare the homologous heterologous regimens targeting Nef-Tat fusion antigen develop a human immunodeficiency virus-1 (HIV-1) therapeutic candidate.

Language: Английский

Citations

1