Dataset Information

IFNα induces CCR5 in CD4⁺ T cells of HIV patients causing pathogenic elevation.

ABSTRACT:

Background

Among people living with HIV, elite controllers (ECs) maintain an undetectable viral load, even without receiving anti-HIV therapy. In non-EC patients, this therapy leads to marked improvement, including in immune parameters, but unlike ECs, non-EC patients still require ongoing treatment and experience co-morbidities. In-depth, comprehensive immune analyses comparing EC and treated non-EC patients may reveal subtle, consistent differences. This comparison could clarify whether elevated circulating interferon-alpha (IFNα) promotes widespread immune cell alterations and persists post-therapy, furthering understanding of why non-EC patients continue to need treatment.

Methods

Levels of IFNα in HIV-infected EC and treated non-EC patients were compared, along with blood immune cell subset distribution and phenotype, and functional capacities in some cases. In addition, we assessed mechanisms potentially associated with IFNα overload.

Results

Treatment of non-EC patients results in restoration of IFNα control, followed by marked improvement in distribution numbers, phenotypic profiles of blood immune cells, and functional capacity. These changes still do not lead to EC status, however, and IFNα can induce these changes in normal immune cell counterparts in vitro. Hypothesizing that persistent alterations could arise from inalterable effects of IFNα at infection onset, we verified an IFNα-related mechanism. The protein induces the HIV coreceptor CCR5, boosting HIV infection and reducing the effects of anti-HIV therapies. EC patients may avoid elevated IFNα following on infection with a lower inoculum of HIV or because of some unidentified genetic factor.

Conclusions

Early control of IFNα is essential for better prognosis of HIV-infected patients.

SUBMITTER: Le Buanec H

PROVIDER: S-EPMC10951336 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

IFNα induces CCR5 in CD4<sup>+</sup> T cells of HIV patients causing pathogenic elevation.

Le Buanec Hélène H Schiavon Valérie V Merandet Marine M How-Kit Alexandre A Song Hongshuo H Bergerat David D Fombellida-Lopez Céline C Bensussan Armand A Bouaziz Jean-David JD Burny Arsène A Darcis Gilles G Sajadi Mohammad M MM Kottilil Shyamasundaran S Zagury Daniel D Gallo Robert C RC

Communications medicine 20240319 1

<h4>Background</h4>Among people living with HIV, elite controllers (ECs) maintain an undetectable viral load, even without receiving anti-HIV therapy. In non-EC patients, this therapy leads to marked improvement, including in immune parameters, but unlike ECs, non-EC patients still require ongoing treatment and experience co-morbidities. In-depth, comprehensive immune analyses comparing EC and treated non-EC patients may reveal subtle, consistent differences. This comparison could clarify whethe ...[more]

PMID: 38504093

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Project description:The interactions between a virus and its host are complex but can be broadly categorized as either viral manipulation of cellular functions or cellular responses to infection. These processes begin at the earliest point of contact between virus and cell and frequently result in changes to cellular gene expression, making genome-wide transcriptomics a useful tool to study them. Several previous studies have used transcriptomics to evaluate the cellular responses to human immunodeficiency virus type 1 (HIV-1) infection; however, none have examined events in primary CD4+ T cells during the first 24 h of infection. Here, we analyzed CD4+ T cells at 4.5, 8, 12, 24, and 48 h following infection. We describe global changes to host gene expression commencing at 4.5 h postinfection and evolving over the ensuing time points. We identify upregulation of genes related to innate immunity, cytokine production, and apoptosis and downregulation of those involved in transcription and translation. We further demonstrate that the viral accessory protein Vpr is necessary for almost all gene expression changes seen at 12 h postinfection and the majority of those seen at 48 h. Identifying this new role for Vpr not only provides fresh perspective on its possible function but also adds further insight into the interplay between HIV-1 and its host at the cellular level. IMPORTANCE HIV-1, while now treatable, remains an important human pathogen causing significant morbidity and mortality globally. The virus predominantly infects CD4+ T cells and, if not treated with medication, ultimately causes their depletion, resulting in AIDS and death. Further refining our understanding of the interaction between HIV-1 and these cells has the potential to inform further therapeutic development. Previous studies have used transcriptomics to assess gene expression changes in CD4+ T cells following HIV-1 infection; here, we provide a detailed examination of changes occurring in the first 24 h of infection. Importantly, we define the viral protein Vpr as essential for the changes observed at this early stage. This finding has significance for understanding the role of Vpr in infection and pathogenesis and also for interpreting previous transcriptomic analyses of HIV-1 infection.

Dataset Information

IFNα induces CCR5 in CD4⁺ T cells of HIV patients causing pathogenic elevation.

Background

Methods

Results

Conclusions

Publications

IFNα induces CCR5 in CD4<sup>+</sup> T cells of HIV patients causing pathogenic elevation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

IFNα induces CCR5 in CD4+ T cells of HIV patients causing pathogenic elevation.

Background

Methods

Results

Conclusions

Publications

IFNα induces CCR5 in CD4<sup>+</sup> T cells of HIV patients causing pathogenic elevation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

IFNα induces CCR5 in CD4⁺ T cells of HIV patients causing pathogenic elevation.