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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-024-00453-7 |
| _version_ | 1797247072366231552 |
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| author | Hélène Le Buanec Valérie Schiavon Marine Merandet Alexandre How-Kit Hongshuo Song David Bergerat Céline Fombellida-Lopez Armand Bensussan Jean-David Bouaziz Arsène Burny Gilles Darcis Mohammad M. Sajadi Shyamasundaran Kottilil Daniel Zagury Robert C. Gallo |
| author_facet | Hélène Le Buanec Valérie Schiavon Marine Merandet Alexandre How-Kit Hongshuo Song David Bergerat Céline Fombellida-Lopez Armand Bensussan Jean-David Bouaziz Arsène Burny Gilles Darcis Mohammad M. Sajadi Shyamasundaran Kottilil Daniel Zagury Robert C. Gallo |
| author_sort | Hélène Le Buanec |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T19:52:53Z |
| format | Article |
| id | doaj.art-7a6160af375a4badbc2386bf1f9eaf4f |
| institution | Directory Open Access Journal |
| issn | 2730-664X |
| language | English |
| last_indexed | 2024-04-24T19:52:53Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj.art-7a6160af375a4badbc2386bf1f9eaf4f2024-03-24T12:31:54ZengNature PortfolioCommunications Medicine2730-664X2024-03-014111310.1038/s43856-024-00453-7IFNα induces CCR5 in CD4+ T cells of HIV patients causing pathogenic elevationHélène Le Buanec0Valérie Schiavon1Marine Merandet2Alexandre How-Kit3Hongshuo Song4David Bergerat5Céline Fombellida-Lopez6Armand Bensussan7Jean-David Bouaziz8Arsène Burny9Gilles Darcis10Mohammad M. Sajadi11Shyamasundaran Kottilil12Daniel Zagury13Robert C. Gallo14Université de Paris; INSERM U976, HIPI Unit, Institut de Recherche Saint-LouisUniversité de Paris; INSERM U976, HIPI Unit, Institut de Recherche Saint-LouisUniversité de Paris; INSERM U976, HIPI Unit, Institut de Recherche Saint-LouisLaboratory for Genomics Foundation Jean Dausset-CEPHInstitute of Human Virology, School of Medicine, University of MarylandUniversité de Paris; INSERM U976, HIPI Unit, Institut de Recherche Saint-LouisLaboratory of Infectious Diseases, GIGA-I3, GIGA-Institute University of LiegeUniversité de Paris; INSERM U976, HIPI Unit, Institut de Recherche Saint-LouisUniversité de Paris; INSERM U976, HIPI Unit, Institut de Recherche Saint-LouisLaboratory of Molecular Biology, Gembloux Agrobiotech, University of LiègeLaboratory of Infectious Diseases, GIGA-I3, GIGA-Institute University of LiegeInstitute of Human Virology, School of Medicine, University of MarylandInstitute of Human Virology, School of Medicine, University of Maryland21CBIOInstitute of Human Virology, School of Medicine, University of MarylandAbstract 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.https://doi.org/10.1038/s43856-024-00453-7 |
| spellingShingle | Hélène Le Buanec Valérie Schiavon Marine Merandet Alexandre How-Kit Hongshuo Song David Bergerat Céline Fombellida-Lopez Armand Bensussan Jean-David Bouaziz Arsène Burny Gilles Darcis Mohammad M. Sajadi Shyamasundaran Kottilil Daniel Zagury Robert C. Gallo IFNα induces CCR5 in CD4+ T cells of HIV patients causing pathogenic elevation Communications Medicine |
| title | IFNα induces CCR5 in CD4+ T cells of HIV patients causing pathogenic elevation |
| title_full | IFNα induces CCR5 in CD4+ T cells of HIV patients causing pathogenic elevation |
| title_fullStr | IFNα induces CCR5 in CD4+ T cells of HIV patients causing pathogenic elevation |
| title_full_unstemmed | IFNα induces CCR5 in CD4+ T cells of HIV patients causing pathogenic elevation |
| title_short | IFNα induces CCR5 in CD4+ T cells of HIV patients causing pathogenic elevation |
| title_sort | ifnα induces ccr5 in cd4 t cells of hiv patients causing pathogenic elevation |
| url | https://doi.org/10.1038/s43856-024-00453-7 |
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