The reservoir of latent HIV

Frontiers in Cellular and Infection Microbiology, Journal Year: 2022, Volume and Issue: 12

Published: July 28, 2022

The persistence of latent reservoir the human immunodeficiency virus (HIV) is currently major challenge in curing HIV infection. After infects body, unable to be recognized by body’s immune system. Currently, widely adopted antiretroviral therapy (ART) also unble eliminate it, thus hindering progress treatment. This review discusses existence vault for treatment, its formation and factors affecting formation, cell, tissue localization, methods detection removing reservoir, provide a comprehensive understanding vault, order assist future research play potential role achieving

Language: Английский

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Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral profiles

Biomaterials, Journal Year: 2017, Volume and Issue: 151, P. 53 - 65

Published: Oct. 16, 2017

Long-acting parenteral (LAP) antiretroviral drugs have generated considerable interest for treatment and prevention of HIV-1 infection. One new LAP is cabotegravir (CAB), a highly potent integrase inhibitor, with half-life up to 54 days, allowing every other month administrations. Despite this excellent profile, high volume dosing, injection site reactions low body fluid drug concentrations affect broad use virus infected susceptible people. To improve the delivery we created myristoylated CAB prodrug (MCAB). MCAB formed crystals that were formulated into nanoparticles (NMCAB) stable size shape facilitating avid monocyte-macrophage entry, retention reticuloendothelial system depot formulation. Drug release kinetics paralleled sustained protection against challenge. After single 45 mg/kg intramuscular BALB/cJ mice, NMCAB pharmacokinetic profiles was 4-times greater than recorded LAP. These observations replicate measurements in rhesus macaques. The results coupled improved viral restriction human adult lymphocyte reconstituted NOD/SCID/IL2Rγc-/- mice led us conclude can biodistribution clearance upon current formulations.

Language: Английский

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Eradication of HIV-1 from the Macrophage Reservoir: An Uncertain Goal?

Viruses, Journal Year: 2015, Volume and Issue: 7(4), P. 1578 - 1598

Published: March 31, 2015

Human immunodeficiency virus type 1 (HIV-1) establishes latency in resting memory CD4+ T cells and of myeloid lineage. In contrast to the cells, lineage are resistant HIV-1 induced cytopathic effect. Cells including macrophages present anatomical sanctuaries making them a difficult drug target. addition, long life span as compared make important viral reservoirs infected individuals especially late stage infection where largely depleted. past decade, persistence has gained considerable attention. It is currently believed that rebound viremia following cessation combination anti-retroviral therapy (cART) originates from this source. However, clinical relevance reservoir been questioned. suggested only one source residual other such tissue should be seriously considered. review we will discuss how contribute development long-lived latent can used therapeutic target eradicating reservoir.

Language: Английский

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CRISPR-Cas based antiviral strategies against HIV-1

Virus Research, Journal Year: 2017, Volume and Issue: 244, P. 321 - 332

Published: July 29, 2017

In bacteria and archaea, the clustered regularly interspaced short palindromic repeats (CRISPR) associated proteins (Cas) confer adaptive immunity against exogenous DNA elements. This CRISPR-Cas system has been turned into an effective tool for editing of eukaryotic genomes. Pathogenic viruses that have a double-stranded (dsDNA) genome or replicate through dsDNA intermediate can also be targeted with this tool. Here, we review how was used in novel therapeutic approaches human immunodeficiency virus type-1 (HIV-1), focusing on aim to permanently inactivate all genomes prevent viral persistence latent reservoirs.

Language: Английский

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Exosomes from uninfected cells activate transcription of latent HIV-1

Journal of Biological Chemistry, Journal Year: 2017, Volume and Issue: 292(28), P. 11682 - 11701

Published: May 24, 2017

HIV-1 infection causes AIDS, infecting millions worldwide. The virus can persist in a state of chronic due to its ability become latent. We have previously shown link between and exosome production. Specifically, we reported that exosomes transport viral proteins RNA from infected cells neighboring uninfected cells. These products could then elicit an innate immune response, leading activation the Toll-like receptor NF-κB pathways. In this study, asked whether activate latent observed irrespective combination antiretroviral therapy, both short- long-length transcripts were increased wild-type HIV-1-infected exposed purified A search for possible mechanism finding revealed increase polymerase II loading onto promoter transcripts, which include trans-activation response (TAR) novel termed TAR-gag, be packaged into potentially exported cells, cellular activation. To better decipher release pathways involved, used siRNA suppress expression ESCRT (endosomal sorting complex required transport) found IV significantly control release. Collectively, these results imply true transcriptional latency may not vivo, especially presence therapy.

Language: Английский

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Role of the macrophage in HIV-associated neurocognitive disorders and other comorbidities in patients on effective antiretroviral treatment

Journal of NeuroVirology, Journal Year: 2015, Volume and Issue: 21(3), P. 235 - 241

Published: May 1, 2015

Language: Английский

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Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids

Scientific Reports, Journal Year: 2018, Volume and Issue: 8(1)

Published: Jan. 4, 2018

Abstract Cholestasis is caused by autoimmune reactions, drug-induced hepatotoxicity, viral infections of the liver and obstruction bile ducts tumours or gallstones. Cholestatic conditions are associated with impaired innate adaptive immunity, including alterations cellular functions monocytes, macrophages, NK cells T-cells. Bile acids act as signalling molecules, affecting lipopolysaccharide (LPS)-induced cytokine expression in primary human macrophages. The present manuscript investigates impact acids, such taurolithocholic acid (TLC), on transcriptome macrophages presence absence LPS. While TLC itself has almost no effect gene under control conditions, this compound modulates 202 out 865 transcripts Interestingly, pathway analysis revealed that specifically supressed genes involved mediating pro-inflammatory effects, phagocytosis, interactions pathogens autophagy well recruitment immune cells, neutrophils T cells. These data indicate a broad influence inflammatory responses findings may contribute to clinical observation patients cholestasis lack response bacterial infections.

Language: Английский

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Expression and regulation of Schlafen (SLFN) family members in primary human monocytes, monocyte-derived dendritic cells and T cells

Results in Immunology, Journal Year: 2015, Volume and Issue: 5, P. 23 - 32

Published: Jan. 1, 2015

Schlafen (SLFN/Slfn) family members have been investigated for their involvement in fundamental cellular processes including growth regulation, differentiation and control of viral replication. However, most research has focused on the characterization Slfns within murine system or human cell lines. Since little is known about SLFNs primary immune cells, we set out to analyze expression regulation six SLFN genes monocytes, monocyte-derived dendritic cells (moDCs) T cells. Comparison gene across these three types showed high mRNA SLFN11 monocytes moDCs SLFN5 indicating functional importance types. Differentiation leads gradual upregulation SLFN12L SLFN13 while SLFN12 levels were decreased by stimuli. Stimulation via rhinovirus, lipopolysaccharide, IFN-α lead strong expression, peptidoglycan poorly stimulated both classical interferon-stimulated MxA. activation was found downregulate SLFN5, SLFN12L, which reversible upon addition exogenous IFN-α. In conclusion, demonstrate, that mainly dependent autocrine type I interferon signaling Rapid decrease following receptor stimulation indicates a role quiescence.

Language: Английский

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Single-Particle Tracking of Human Immunodeficiency Virus Type 1 Productive Entry into Human Primary Macrophages

ACS Nano, Journal Year: 2017, Volume and Issue: 11(4), P. 3890 - 3903

Published: April 4, 2017

Macrophages are one of the major targets human immunodeficiency virus (HIV-1), but viral entry pathway remains poorly understood in these cells. Noninvasive labeling and single-virus tracking effective tools for studying entry. Here, we constructed a quantum dot (QD)-encapsulated infectious HIV-1 particle to track at single-particle level live primary macrophages. QDs were encapsulated virions by incorporating accessory protein Vpr-conjugated during assembly. With particles encapsulating QDs, monitored early phase infection real time observed that, infection, was endocytosed clathrin-mediated manner; translocated into Rab5A-positive endosomes, core released cytoplasm envelope-mediated endosomal fusion. Drug inhibition assays verified that endosome fusion contributes productive Additionally, dynamic actin cytoskeleton is critical intracellular migration dynamics could be blocked multiple different inhibitors. Our study revealed macrophages requires both function dynamics, which may assist development inhibitors block HIV

Language: Английский

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Myeloid Cell Interaction with HIV: A Complex Relationship

Frontiers in Immunology, Journal Year: 2017, Volume and Issue: 8

Published: Nov. 30, 2017

Cells of the myeloid lineage, particularly macrophages, serve as primary hosts for HIV in vivo, along with CD4 T lymphocytes. Macrophages are present virtually every tissue organism, including locations negligible cell colonization, such brain, where HIV-mediated inflammation may lead to pathological sequelae. Moreover, infected macrophages multiple other tissues. Recent evidence obtained humanized mice and macaque models highlighted capacity sustain replication vivo absence cells. Combined known resistance macrophage cytopathic effects infection, data brings a renewed interest this type both vehicle viral spread well reservoir. While our understanding key processes infection is far from complete, recent years have nevertheless brought important insight into uniqueness infection. Productive by can occur different routes phagocytosis In assembles buds peculiar plasma-membrane-connected compartment that pre-exists function remains elusive, it supposedly allows persistence infectious particles over extended periods time play role on transmission. As cells innate immune system, detect respond components. suggest sensing at steps cycle impact subsequent spread. We aim provide an overview HIV-macrophage interaction stages life cycle, extending when pertinent observations additional types dendritic or blood monocytes.

Language: Английский

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