scholarly journals Effects of exosome on the activation of CD4+ T cells in rhesus macaques: a potential application for HIV latency reactivation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaowu Hong ◽  
Blake Schouest ◽  
Huanbin Xu
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Potential Application ◽  
Rhesus Macaques ◽  
Hiv Latency

scholarly journals Probiotic supplementation reduces inflammatory profiles but does not prevent oral immune perturbations during SIV infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rhianna Jones ◽  
Kyle Kroll ◽  
Courtney Broedlow ◽  
Luca Schifanella ◽  
Scott Smith ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Rhesus Macaques ◽  
Oral Microbiome ◽  
Probiotic Supplementation ◽  
Siv Infection ◽  
Anti Inflammatory

AbstractHIV/SIV infections lead to massive loss of mucosal CD4 + T cells and breakdown of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one of the most understudied mucosal environments, the oral cavity, during HIV-induced immunosuppression results in significant microbial and neoplastic co-morbidities and contributes to and predicts distal disease complications. In this study we evaluated the effects of oral probiotic supplementation (PBX), which can stimulate and augment inflammatory or anti-inflammatory pathways, on early SIV infection of rhesus macaques. Our study revealed that similar to the GI mucosae, oral CD4 + T cells were rapidly depleted, and as one of the first comprehensive analyses of the oral microflora in SIV infection, we also observed significant modulation among two genera, Porphyromonas and Actinobacillus, early after infection. Interestingly, although PBX therapy did not substantially protect against oral dysbiosis or ameliorate cell loss, it did somewhat dampen inflammation and T cell activation. Collectively, these data provide one of the most comprehensive evaluations of SIV-induced changes in oral microbiome and CD4 + T cell populations, and also suggest that oral PBX may have some anti-inflammatory properties in lentivirus infections.

scholarly journals Functional Impairment of Central Memory CD4 T Cells Is a Potential Early Prognostic Marker for Changing Viral Load in SHIV-Infected Rhesus Macaques

PLoS ONE ◽  
2011 ◽  
Vol 6 (5) ◽  
pp. e19607 ◽  
Author(s):  
Hong He ◽  
Pramod N. Nehete ◽  
Bharti Nehete ◽  
Eric Wieder ◽  
Guojun Yang ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
Prognostic Marker ◽  
Functional Impairment ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
Central Memory ◽  
Memory Cd4 T Cells

scholarly journals Author response: Distinct chromatin functional states correlate with HIV latency reactivation in infected primary CD4+ T cells

2018 ◽  
Author(s):  
Emilie Battivelli ◽  
Matthew S Dahabieh ◽  
Mohamed Abdel-Mohsen ◽  
J Peter Svensson ◽  
Israel Tojal Da Silva ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Author Response ◽  
Hiv Latency ◽  
Functional States

scholarly journals Biogenesis of P-TEFb in CD4+ T cells to reverse HIV latency is mediated by protein kinase C (PKC)-independent signaling pathways

2021 ◽  
Author(s):  
Uri Mbonye ◽  
Konstantin Leskov ◽  
Meenakshi Shukla ◽  
Saba Valadkhan ◽  
Jonathan Karn
Keyword(s):  
T Cells ◽  
Protein Kinase C ◽  
T Cell ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Cd4 T Cells ◽  
Hiv Latency ◽  
Kinase C ◽  
Latent Hiv ◽  
Memory Cd4 T Cells

The switch between HIV latency and productive transcription is regulated by an auto-feedback mechanism initiated by the viral trans-activator Tat, which functions to recruit the host transcription elongation factor P-TEFb to proviral HIV. A heterodimeric complex of CDK9 and one of three cyclin T subunits, P-TEFb is expressed at vanishingly low levels in resting memory CD4 + T cells and cellular mechanisms controlling its availability are central to regulation of the emergence of HIV from latency. Using a well-characterized primary T-cell model of HIV latency alongside healthy donor memory CD4 + T cells, we characterized specific T-cell receptor (TCR) signaling pathways that regulate the generation of transcriptionally active P-TEFb, defined as the coordinate expression of cyclin T1 and phospho-Ser175 CDK9. Protein kinase C (PKC) agonists, such as ingenol and prostratin, stimulated active P-TEFb expression and reactivated latent HIV with minimal cytotoxicity, even in the absence of intracellular calcium mobilization with an ionophore. Unexpectedly, inhibition-based experiments demonstrated that PKC agonists and TCR-mobilized diacylglycerol signal through MAP kinases ERK1/2 rather than through PKC to effect the reactivation of both P-TEFb and latent HIV. Single-cell and bulk RNA-seq analyses revealed that of the four known isoforms of the Ras guanine nucleotide exchange factor RasGRP, RasGRP1 is by far the predominantly expressed diacylglycerol-dependent isoform in CD4 + T cells. RasGRP1 should therefore mediate the activation of ERK1/2 via Ras-Raf signaling upon TCR co-stimulation or PKC agonist challenge. Combined inhibition of the PI3K-mTORC2-AKT-mTORC1 pathway and the ERK1/2 activator MEK prior to TCR co-stimulation abrogated active P-TEFb expression and substantially suppressed latent HIV reactivation. Therefore, contrary to prevailing models, the coordinate reactivation of P-TEFb and latent HIV in primary T cells following either TCR co-stimulation or PKC agonist challenge is independent of PKC but rather involves two complementary signaling arms of the TCR cascade, namely, RasGRP1-Ras-Raf-MEK-ERK1/2 and PI3K-mTORC2-AKT-mTORC1.

scholarly journals HIV latency in isolated patient CD4+T cells may be due to blocks in HIV transcriptional elongation, completion, and splicing

2018 ◽  
Vol 10 (430) ◽  
pp. eaap9927 ◽  
Author(s):  
Steven A. Yukl ◽  
Philipp Kaiser ◽  
Peggy Kim ◽  
Sushama Telwatte ◽  
Sunil K. Joshi ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Hiv Latency ◽  
Transcriptional Elongation

scholarly journals Correction: Minimally invasive monitoring of CD4 T cells at multiple mucosal tissues after intranasal vaccination in rhesus macaques

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191378
Author(s):  
Stephanie Dorta-Estremera ◽  
Pramod N. Nehete ◽  
Guojun Yang ◽  
Hong He ◽  
Bharti P. Nehete ◽  
...  
Keyword(s):  
T Cells ◽  
Minimally Invasive ◽  
Cd4 T Cells ◽  
Rhesus Macaques ◽  
Invasive Monitoring ◽  
Mucosal Tissues

scholarly journals Single-cell transcriptomics to evaluate HIV latency establishment in primary CD4 T cells

2017 ◽  
Vol 3 ◽  
pp. 11
Author(s):  
L. De Armas ◽  
S. Williams ◽  
K. Russell ◽  
L. Pan ◽  
S. Pahwa
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Cd4 T Cells ◽  
Hiv Latency

scholarly journals Probiotic Supplementation Reduces Inflammatory Profiles But Does Not Prevent Oral Immune Perturbations During SIV Infection

2020 ◽  
Author(s):  
Rhianna Jones ◽  
Kyle Kroll ◽  
Courtney Broedlow ◽  
Luca Schifanella ◽  
Scott Smith ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Rhesus Macaques ◽  
Oral Microbiome ◽  
Probiotic Supplementation ◽  
Siv Infection ◽  
Anti Inflammatory

ABSTRACTHIV/SIV infections lead to massive loss of mucosal CD4+ T cells and breakdown of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one of the most understudied mucosal environments, the oral cavity, during HIV-induced immunosuppression results in significant microbial and neoplastic co-morbidities and contributes to and predicts distal disease complications. In this study we evaluated the effects of oral probiotic supplementation (Pbx), which can stimulate and augment inflammatory or anti-inflammatory pathways, on early SIV infection of rhesus macaques. Our study revealed that similar to the GI mucosae, oral CD4+ T cells were rapidly depleted, and as one of the first comprehensive analyses of the oral microflora in SIV infection, we also observed significant modulation among two genera, Porphyromonas and Actinobacillus, early after infection. Interestingly, although Pbx therapy did not substantially protect against oral dysbiosis or ameliorate cell loss, it did dampen inflammation and T cell activation. Collectively, these data provide one of the most comprehensive evaluations of SIV-induced changes in oral microbiome and CD4+ T cell populations, and also suggest that oral Pbx could be a simple therapy to improve anti-inflammatory states in addition to more traditional antivirals.

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