Longitudinal regulation over time of gene expression in mock infected and HIV-1 infected CD4+ T-cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE163405 | GEO | 2021/06/14
REPOSITORIES: GEO
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Project description:Quiescence is a hallmark of CD4+ T cells latently infected with HIV-1. While reversing this quiescence is an effective approach to reactivate latent HIV from T cells in culture, it can cause deleterious cytokine dysregulation in patients. Here we report that FOXO1, a key regulator of T-cell quiescence, promotes latency and suppresses productive HIV infection. In resting T cells, FOXO1 inhibition induces ER stress and activates two associated transcription factors: activating transcription factor 4 (ATF4) and nuclear factor of activated T cells (NFAT). Thus, our studies uncover a novel link between FOXO1, ER stress, and HIV infection that could be therapeutically exploited to selectively reverse T-cell quiescence and reduce the size of the latent viral reservoir.
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Project description:Aguilera 2014 - HIV latency. Interaction
between HIV proteins and immune response
This model is described in the article:
Studying HIV latency by
modeling the interaction between HIV proteins and the innate
immune response.
Aguilera LU,
Rodríguez-González J.
J. Theor. Biol. 2014 Nov; 360:
67-77
Abstract:
HIV infection leads to two cell fates, the viral productive
state or viral latency (a reversible non-productive state). HIV
latency is relevant because infected active CD4+ T-lymphocytes
can reach a resting memory state in which the provirus remains
silent for long periods of time. Despite experimental and
theoretical efforts, the causal molecular mechanisms
responsible for HIV latency are only partially understood.
Studies have determined that HIV latency is influenced by the
innate immune response carried out by cell restriction factors
that inhibit the postintegration steps in the virus replication
cycle. In this study, we present a mathematical study that
combines deterministic and stochastic approaches to analyze the
interactions between HIV proteins and the innate immune
response. Using wide ranges of parameter values, we observed
the following: (1) a phenomenological description of the viral
productive and latent cell phenotypes is obtained by bistable
and bimodal dynamics, (2) biochemical noise reduces the
probability that an infected cell adopts the latent state, (3)
the effects of the innate immune response enhance the HIV
latency state, (4) the conditions of the cell before infection
affect the latent phenotype, i.e., the existing expression of
cell restriction factors propitiates HIV latency, and existing
expression of HIV proteins reduces HIV latency.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000573.
To cite BioModels Database, please use:
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To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
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Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000573 | BioModels
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Project description:Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for HIV infection. Here, we implement a systems approach to discover molecular signatures of HIV latently-infected CD4+ T cells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increases the frequency of CD73+ CD4+ T cells and promotes HIV latency. Transcriptomic profiles of CD73+ CD4+ T cells favor viral quiescence, immune evasion, and cell survival. CD73+ CD4+ T cells are capable of harboring a functional HIV reservoir and reinitiating productive infection ex vivo. CD73 or adenosine receptor blockade facilitates latent HIV reactivation in vitro, mechanistically linking adenosine signaling to viral quiescence. Finally, tissue imaging of lymph nodes from HIV-infected individuals on antiretroviral therapy reveals spatial association between CD73 expression and HIV persistence in vivo. Our findings warrant development of HIV cure strategies targeting the hypoxia-CD73-adenosine axis.
2023-09-28 | GSE244190 | GEO
Project description:Latent HIV-1 infection represents a barrier to virus eradication as latent HIV-1 is impervious to the effects of antiretroviral drugs and can avoid detection by the host immune system. Strategies to clear latent HIV-1 infection in patients have so far failed in clinical trials to increase the decay rate of the latent reservoir underscoring the need for continued study of HIV-1 latency. In this study, a genome-wide RNAi screen was performed to probe cellular factors involved in maintaining HIV-1 latency in HeLa cells latently infected with an HIV-1 reporter virus.
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