scholarly journals The Per-1 Short Isoform Inhibits de novo HIV-1 Transcription in Resting CD4+ T-cells

2019 ◽  
Vol 16 (6) ◽  
pp. 384-395 ◽  
Author(s):  
Li Zhao ◽  
Mei Liu ◽  
Jiayue Ouyang ◽  
Zheming Zhu ◽  
Wenqing Geng ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
De Novo ◽  
Inhibitory Effect ◽  
Negative Regulator ◽  
Viral Loads ◽  
Transcription Blockage ◽  
Negative Factors ◽  
Hiv 1

Background: Understanding of the restriction of HIV-1 transcription in resting CD4+ Tcells is critical to find a cure for AIDS. Although many negative factors causing HIV-1 transcription blockage in resting CD4+ T-cells have been found, there are still unknown mechanisms to explore. Objective: To explore the mechanism for the suppression of de novo HIV-1 transcription in resting CD4+ T-cells. Methods: In this study, a short isoform of Per-1 expression plasmid was transfected into 293T cells with or without Tat's presence to identify Per-1 as a negative regulator for HIV-1 transcription. Silencing of Per-1 was conducted in resting CD4+ T-cells or monocyte-derived macrophages (MDMs) to evaluate the antiviral activity of Per-1. Additionally, we analyzed the correlation between Per-1 expression and viral loads in vivo, and silenced Per-1 by siRNA technology to investigate the potential anti-HIV-1 roles of Per-1 in vivo in untreated HIV-1-infected individuals. Results: We found that short isoform Per-1 can restrict HIV-1 replication and Tat ameliorates this inhibitory effect. Silencing of Per-1 could upregulate HIV-1 transcription both in resting CD4+ Tcells and MDMs. Moreover, Per-1 expression is inversely correlated with viral loads in Rapid progressors (RPs) in vivo. Conclusion: These data together suggest that Per-1 is a novel negative regulator of HIV-1 transcription. This restrictive activity of Per-1 to HIV-1 replication may contribute to HIV-1 latency in resting CD4+ T-cells.

scholarly journals Preferential infection and depletion of Mycobacterium tuberculosis–specific CD4 T cells after HIV-1 infection

2010 ◽  
Vol 207 (13) ◽  
pp. 2869-2881 ◽  
Author(s):  
Christof Geldmacher ◽  
Njabulo Ngwenyama ◽  
Alexandra Schuetz ◽  
Constantinos Petrovas ◽  
Klaus Reither ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Hiv Infection ◽  
Cd4 T Cells ◽  
Staphylococcal Enterotoxin B ◽  
Opportunistic Pathogens ◽  
Rapid Loss ◽  
Hiv 1

HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific CD4 T cells are affected by HIV infection and the cellular parameters involved. We found striking differences in the depletion rates between CD4 T cells to two common opportunistic pathogens, cytomegalovirus (CMV) and Mycobacterium tuberculosis (MTB). CMV-specific CD4 T cells persisted after HIV infection, whereas MTB-specific CD4 T cells were depleted rapidly. CMV-specific CD4 T cells expressed a mature phenotype and produced very little IL-2, but large amounts of MIP-1β. In contrast, MTB-specific CD4 T cells were less mature, and most produced IL-2 but not MIP-1β. Staphylococcal enterotoxin B–stimulated IL-2–producing cells were more susceptible to HIV infection in vitro than MIP-1β–producing cells. Moreover, IL-2 production was associated with expression of CD25, and neutralization of IL-2 completely abrogated productive HIV infection in vitro. HIV DNA was found to be most abundant in IL-2–producing cells, and least abundant in MIP-1β–producing MTB-specific CD4 T cells from HIV-infected subjects with active tuberculosis. These data support the hypothesis that differences in function affect the susceptibility of pathogen-specific CD4 T cells to HIV infection and depletion in vivo, providing a potential mechanism to explain the rapid loss of MTB-specific CD4 T cells after HIV infection.

scholarly journals HIV-1 Vpr Accelerates Viral Replication during Acute Infection by Exploitation of Proliferating CD4+ T Cells In Vivo

2013 ◽  
Vol 9 (12) ◽  
pp. e1003812 ◽  
Author(s):  
Kei Sato ◽  
Naoko Misawa ◽  
Shingo Iwami ◽  
Yorifumi Satou ◽  
Masao Matsuoka ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Replication ◽  
Cd4 T Cells ◽  
Acute Infection ◽  
Hiv 1

Identification of a Discrete Subpopulation of T-Cells Over-Expressing HDAC11 with a TH17 Phenotype

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 588-588
Author(s):  
Karrune Woan ◽  
Fengdong Cheng ◽  
Hongwei Wang ◽  
Jennifer Rock-Klotz ◽  
Zi Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Function ◽  
Conflicts Of Interest ◽  
Negative Regulator ◽  
Egfp Expression ◽  
In Vivo Models

Abstract Abstract 588 We recently defined a novel role of histone deacetylase 11 (HDAC11), the newest member of the HDAC family, as a negative regulator of IL-10 gene transcription in antigen-presenting cells (APCs).1 To better understand the role of HDAC11 gene expression in immune cells in vivo, we have utilized a BAC (Bacterial artificial chromosome) transgenic mouse in which the EGFP reporter gene was inserted downstream of the HDAC11 promoter region but immediately upstream of the HDAC11 coding sequence (TgHDAC11-EGFP mice).2 In the steady-state, macrophages and B-cells isolated from spleen of TgHDAC11-EGFP mice express low levels of HDAC11 as evidenced by a slight shift in EGFP fluorescence from background. In sharp contrast, we identified a discrete population (11.9%) of T-cells over-expressing HDAC11 as demonstrated both by flow cytometry for EGFP and by qRT-PCR for HDAC11, a majority of which were CD4+ T-cells. Sorting of this EGFP+, CD4+ T-cell population confirmed that the increased EGFP expression correlated with an increased HDAC11mRNA expression. Reminiscent of our prior data in APCs, the increased expression of HDAC11 in T-cells was also inversely correlated with IL-10mRNA expression. Further analyses revealed that in the absence of any stimulation or T-cell polarizing conditions, this EGFP positive population expressed significantly elevated levels of ROR-γt and IL-17 mRNA, markers specific for the TH17 subpopulation. Polarization of wild type CD4+ T-cells into functional TH17 cells was associated with reduction of HDAC11 expression, suggesting a potential role for HDAC11 in regulating T-cell function and/or activation, in particular within the TH17 subset. Further support for this regulatory role of HDAC11 has been provided by our additional findings that T-cells devoid of HDAC11 are indeed hyper-reactive in vitro and in in vivo models. 1. Villagra A, et al. Nat Immunol. 2009 Jan;10(1):92-100. 2. Gong S, et al. Nature. 2003 Oct 30;425(6961):917-25. Disclosures: No relevant conflicts of interest to declare.

HIV-1-infected CD8+CD4+ T cells decay in vivo at a similar rate to infected CD4 T cells during HAART

AIDS ◽  
2008 ◽  
Vol 22 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Gareth J Hughes ◽  
Alexandra Cochrane ◽  
Clifford Leen ◽  
Sheila Morris ◽  
Jeanne E Bell ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Similar Rate ◽  
Hiv 1

scholarly journals Slow Turnover of HIV-1 Receptors on Quiescent CD4+ T Cells Causes Prolonged Surface Retention of gp120 Immune Complexes In Vivo

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e86479 ◽  
Author(s):  
Yasuhiro Suzuki ◽  
Hiroyuki Gatanaga ◽  
Natsuo Tachikawa ◽  
Shinichi Oka
Keyword(s):  
T Cells ◽  
Immune Complexes ◽  
Cd4 T Cells ◽  
Hiv 1 ◽  
Slow Turnover

scholarly journals Type I Interferon Is a Powerful Inhibitor of in Vivo HIV-1 Infection and Preserves Human CD4+ T Cells from Virus-Induced Depletion in SCID Mice Transplanted with Human Cells

Virology ◽  
1999 ◽  
Vol 263 (1) ◽  
pp. 78-88 ◽  
Author(s):  
Caterina Lapenta ◽  
Stefano M. Santini ◽  
Enrico Proietti ◽  
Paola Rizza ◽  
Mariantonia Logozzi ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Type I Interferon ◽  
Human Cells ◽  
Scid Mice ◽  
Type I ◽  
Hiv 1

scholarly journals In vivo HIV-1 infection of CD45RA+CD4+ T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4+ T cell decline

2000 ◽  
Vol 97 (3) ◽  
pp. 1269-1274 ◽  
Author(s):  
H. Blaak ◽  
A. B. van't Wout ◽  
M. Brouwer ◽  
B. Hooibrink ◽  
E. Hovenkamp ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cell Decline ◽  
Hiv 1

Initial evaluation of oncoretroviral vectors carrying HIV-1 inhibitor gene into rhesus CD34+ cells and/or CD4+ T cells: An in vivo model for the gene therapy of AIDS

2008 ◽  
Vol 40 (2) ◽  
pp. 257
Author(s):  
Stephen E. Braun ◽  
Fay Eng Wong ◽  
Michelle Connole ◽  
Ran Taube ◽  
Akikazu Murakami ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
Cd4 T Cells ◽  
Initial Evaluation ◽  
In Vivo Model ◽  
Cd34 Cells ◽  
Hiv 1 ◽  
Inhibitor Gene

scholarly journals Mapping Rora expression in resting and activated CD4+ T cells

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251233
Author(s):  
Liora Haim-Vilmovsky ◽  
Johan Henriksson ◽  
Jennifer A. Walker ◽  
Zhichao Miao ◽  
Eviatar Natan ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Treg Cells ◽  
Negative Regulator ◽  
Th2 Cells ◽  
Nippostrongylus Brasiliensis ◽  
Rna Seq ◽  
Infection Models

The transcription factor Rora has been shown to be important for the development of ILC2 and the regulation of ILC3, macrophages and Treg cells. Here we investigate the role of Rora across CD4+ T cells in general, but with an emphasis on Th2 cells, both in vitro as well as in the context of several in vivo type 2 infection models. We dissect the function of Rora using overexpression and a CD4-conditional Rora-knockout mouse, as well as a RORA-reporter mouse. We establish the importance of Rora in CD4+ T cells for controlling lung inflammation induced by Nippostrongylus brasiliensis infection, and have measured the effect on downstream genes using RNA-seq. Using a systematic stimulation screen of CD4+ T cells, coupled with RNA-seq, we identify upstream regulators of Rora, most importantly IL-33 and CCL7. Our data suggest that Rora is a negative regulator of the immune system, possibly through several downstream pathways, and is under control of the local microenvironment.

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