Transcriptomic Analysis of mRNAs in Human Monocytic Cells Expressing the HIV-1 Nef Protein and Their Exosomes

Aqil, Madeeha; Mallik, Saurav; Bandyopadhyay, Sanghamitra; Maulik, Ujjwal; Jameel, Shahid

doi:10.1155/2015/492395

Cited by 37 publications

(23 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nef was previously shown to promote its own secretion in exosomes from various cells (Ali et al 2010; Aqil et al 2015; Lenassi et al 2010; Muratori et al 2009; Raymond et al 2016), but there are contradictory reports regarding its release from astrocytes (Raymond et al 2016; Sami Saribas et al 2017). Therefore, we wanted to explore if Nef-exosomes are released from Nef.GFP-expressing astrocytes.…”

Section: Resultsmentioning

confidence: 99%

“…Nef is secreted in exosomes from Nef-expressing Hela.CIITA cells (Lenassi et al 2010), HEK293 cells (Ali et al 2010), T cells (Ali et al 2010; Lenassi et al 2010; Muratori et al 2009), U937 monocytes (Aqil et al 2015), and microglia (Raymond et al 2016). A recent report supports the release of Nef-exosomes from astrocytes transduced with adenovirus construct expressing Nef, but only a trace amount (Sami Saribas et al 2017) or no Nef.GFP (Raymond et al 2016) was detected in exosomes released from Nef.GFP-expressing astrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Nef-exosomes from HIV-1-infected cells were shown to render resting human primary CD4+ T cells permissive to HIV-1 infection (Arenaccio et al 2014) and can activate latent HIV-1 in primary human CD4+ T lymphocytes (Arenaccio et al 2014) and U937 cells (Arenaccio et al 2015). In human monocytes, Nef expression modulates cellular and exosomal miRNA profiles (Aqil et al 2015). Nef-exosomes from Nef-expressing cells trigger apoptosis in bystander T cells (Lenassi et al 2010) and impair the BBB (Raymond et al 2016), while Nef-exosomes isolated from the plasma of individuals with HAD induce the secretion of Aβ from neuroblastoma cell line SH-SY5Y (Khan et al 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Exosomes (30–100 nm in diameter) are formed as intraluminal vesicles in MVBs and released through MVB fusion with the plasma membrane, while microvesicles (100–1000 nm) bud directly from the plasma membrane. Importantly, Nef was detected in exosomes released from Hela.CIITA cells (Lenassi et al 2010), HEK293 cells (Ali et al 2010), T cells (Ali et al 2010; Lenassi et al 2010; Muratori et al 2009), U937 monocytes (Aqil et al 2015), microglia (Raymond et al 2016), and conditionally from astrocytes (Raymond et al 2016; Sami Saribas et al 2017); and Nef-containing EVs were also detected in the plasma of HIV-1-infected patients (Khan et al 2016; Lee et al 2016; Raymond et al 2011). Still, the study by Luo et al raised some concerns about the EV-bound nature of extracellular Nef (Luo et al 2015).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Nef is secreted in exosomes from Nef.GFP-expressing and HIV-1-infected human astrocytes

et al. 2017

View full text Add to dashboard Cite

HIV-1 infection of the central nervous system causes HIV-associated neurocognitive disorders, even in aviremic patients. Although astrocyte malfunction was associated to these disorders, their implication is overshadowed by contributions of microglia and macrophages. Astrocytes are infected with HIV-1 in vivo and express a relevant amount of viral protein Nef. Nef was shown to stimulate its own release in exosomes from diverse cell types, which in turn have damaging effects on neighboring cells. Using immunoblotting and electron microscopy, we showed that human astrocytes expressing Nef.GFP similarly release Nef in exosomes. Importantly, Nef.GFP expression increases the secretion of exosomes from human astrocytes up to 5.5-fold, as determined by total protein content and nanoparticle tracking analysis. Protein analysis of exosomes and viruses separated on iodixanol gradient further showed that native or pseudotyped HIV-1-infected human astrocytes release exosomes, which contain Nef. Our results provide the basis for future studies of the damaging role of Nef-exosomes produced by HIV-infected astrocytes on the central nervous system.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nef is secreted in exosomes from Nef.GFP-expressing and HIV-1-infected human astrocytes

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Besides its well-studied effects on intracellular signaling, Nef also acts through its secretion in exosomes nanovesicles. Nef enhances exosome secretion and entry into uninfected CD4 + T cells, thus leading to apoptotic death [7]. Nef is also responsible for the inhibition of T cell migration in vitro [8].…”

Section: Introductionmentioning

confidence: 99%

HIV-1 Nef promotes migration and chemokine synthesis of human basophils and mast cells through the interaction with CXCR4

et al. 2016

View full text Add to dashboard Cite

BackgroundThe Nef protein can be detected in plasma of HIV-1-infected patients and plays a role in the pathogenesis of HIV-1. Nef produced during the early stages of infection is fundamental in creating the ideal environment for viral replication, e.g. by reducing the ability of infected cells to induce an immune response.AimBased on previous experience showing that both Tat and gp41 of HIV-1 are potent chemotactic factors for basophils and mast cells, and gp120 is a powerful stimulus for the release of histamine and cytokines (IL-4 and IL-13) from basophils, in this study we aimed to verify if the HIV Nef protein can exert some effects on basophils and mast cells purified from healthy volunteers through the interaction with the CXCL12 receptor, CXCR4.MethodsBasophils purified from peripheral blood cells of 30 healthy volunteers and mast cells obtained from lung tissue of ten healthy volunteers were tested by flow cytometric analysis, chemotaxis and chemokine production by ELISA assays.ResultsNef is a potent chemoattractant for basophils and lung mast cells obtained from healthy, HIV-1 and HIV-2 seronegative individuals. Incubation of basophils and mast cells with Nef induces the release of chemokines (CXCL8/IL-8 and CCL3/MIP-1α). The chemotactic activity of Nef on basophils and mast cells is mediated by the interaction with CXCR4 receptors, being blocked by preincubation of FcεRI+ cells with an anti-CXCR4 Ab. Stimulation with Nef or CXCL12/SDF-1α, a CXCR4 ligand, desensitizes basophils to a subsequent challenge with an autologous or heterologous stimulus.ConclusionsThese results indicate that Nef, a HIV-1-encoded α-chemokine homolog protein, plays a direct role in basophils and mast cell recruitment and activation at sites of HIV-1 replication, by promoting directional migration of human FcεRI+ cells and the release of chemokines from these cells. Together with our previous results, these data suggest that FcεRI+ cells contribute to the dysregulation of the immune system in HIV-1 infection.

show abstract

Module-Based Knowledge Discovery for Multiple-Cytosine-Variant Methylation Profile

Mallik

Maulik

2018

Soft Computing for Biological Systems

View full text Add to dashboard Cite

Transcriptomic Analysis of mRNAs in Human Monocytic Cells Expressing the HIV-1 Nef Protein and Their Exosomes

Cited by 37 publications

References 46 publications

Nef is secreted in exosomes from Nef.GFP-expressing and HIV-1-infected human astrocytes

Nef is secreted in exosomes from Nef.GFP-expressing and HIV-1-infected human astrocytes

HIV-1 Nef promotes migration and chemokine synthesis of human basophils and mast cells through the interaction with CXCR4

Module-Based Knowledge Discovery for Multiple-Cytosine-Variant Methylation Profile

Contact Info

Product

Resources

About